Search results for: patient safety incidents
Commenced in January 2007
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Edition: International
Paper Count: 6552

Search results for: patient safety incidents

222 Material Handling Equipment Selection Using Fuzzy AHP Approach

Authors: Priyanka Verma, Vijaya Dixit, Rishabh Bajpai

Abstract:

This research paper is aimed at selecting appropriate material handling equipment among the given choices so that the automation level in material handling can be enhanced. This work is a practical case scenario of material handling systems in consumer electronic appliances manufacturing organization. The choices of material handling equipment among which the decision has to be made are Automated Guided Vehicle’s (AGV), Autonomous Mobile Robots (AMR), Overhead Conveyer’s (OC) and Battery Operated Trucks/Vehicle’s (BOT). There is a need of attaining a certain level of automation in order to reduce human interventions in the organization. This requirement of achieving certain degree of automation can be attained by material handling equipment’s mentioned above. The main motive for selecting above equipment’s for study was solely based on corporate financial strategy of investment and return obtained through that investment made in stipulated time framework. Since the low cost automation with respect to material handling devices has to be achieved hence these equipment’s were selected. Investment to be done on each unit of this equipment is less than 20 lakh rupees (INR) and the recovery period is less than that of five years. Fuzzy analytic hierarchic process (FAHP) is applied here for selecting equipment where the four choices are evaluated on basis of four major criteria’s and 13 sub criteria’s, and are prioritized on the basis of weight obtained. The FAHP used here make use of triangular fuzzy numbers (TFN). The inability of the traditional AHP in order to deal with the subjectiveness and impreciseness in the pair-wise comparison process has been improved in the FAHP. The range of values for general rating purposes for all decision making parameters is kept between 0 and 1 on the basis of expert opinions captured on shop floor. These experts were familiar with operating environment and shop floor activity control. Instead of generating exact value the FAHP generates the ranges of values to accommodate the uncertainty in decision-making process. The four major criteria’s selected for the evaluation of choices of material handling equipment’s available are materials, technical capabilities, cost and other features. The thirteen sub criteria’s listed under these following four major criteria’s are weighing capacity, load per hour, material compatibility, capital cost, operating cost and maintenance cost, speed, distance moved, space required, frequency of trips, control required, safety and reliability issues. The key finding shows that among the four major criteria selected, cost is emerged as the most important criteria and is one of the key decision making aspect on the basis of which material equipment selection is based on. While further evaluating the choices of equipment available for each sub criteria it is found that AGV scores the highest weight in most of the sub-criteria’s. On carrying out complete analysis the research shows that AGV is the best material handling equipment suiting all decision criteria’s selected in FAHP and therefore it is beneficial for the organization to carry out automated material handling in the facility using AGV’s.

Keywords: fuzzy analytic hierarchy process (FAHP), material handling equipment, subjectiveness, triangular fuzzy number (TFN)

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221 Biochemical Effects of Low Dose Dimethyl Sulfoxide on HepG2 Liver Cancer Cell Line

Authors: Esra Sengul, R. G. Aktas, M. E. Sitar, H. Isan

Abstract:

Hepatocellular carcinoma (HCC) is a hepatocellular tumor commonly found on the surface of the chronic liver. HepG2 is the most commonly used cell type in HCC studies. The main proteins remaining in the blood serum after separation of plasma fibrinogen are albumin and globulin. The fact that the albumin showed hepatocellular damage and reflect the synthesis capacity of the liver was the main reason for our use. Alpha-Fetoprotein (AFP) is an albumin-like structural embryonic globulin found in the embryonic cortex, cord blood, and fetal liver. It has been used as a marker in the follow-up of tumor growth in various malign tumors and in the efficacy of surgical-medical treatments, so it is a good protein to look at with albumins. We have seen the morphological changes of dimethyl sulfoxide (DMSO) on HepG2 and decided to investigate its biochemical effects. We examined the effects of DMSO, which is used in cell cultures, on albumin, AFP and total protein at low doses. Material Method: Cell Culture: Medium was prepared in cell culture using Dulbecco's Modified Eagle Media (DMEM), Fetal Bovine Serum Dulbecco's (FBS), Phosphate Buffered Saline and trypsin maintained at -20 ° C. Fixation of Cells: HepG2 cells, which have been appropriately developed at the end of the first week, were fixed with acetone. We stored our cells in PBS at + 4 ° C until the fixation was completed. Area Calculation: The areas of the cells are calculated in the ImageJ (IJ). Microscope examination: The examination was performed with a Zeiss Inverted Microscope. Daytime photographs were taken at 40x, 100x 200x and 400x. Biochemical Tests: Protein (Total): Serum sample was analyzed by a spectrophotometric method in autoanalyzer. Albumin: Serum sample was analyzed by a spectrophotometric method in autoanalyzer. Alpha-fetoprotein: Serum sample was analyzed by ECLIA method. Results: When liver cancer cells were cultured in medium with 1% DMSO for 4 weeks, a significant difference was observed when compared with the control group. As a result, we have seen that DMSO can be used as an important agent in the treatment of liver cancer. Cell areas were reduced in the DMSO group compared to the control group and the confluency ratio increased. The ability to form spheroids was also significantly higher in the DMSO group. Alpha-fetoprotein was lower than the values of an ordinary liver cancer patient and the total protein amount increased to the reference range of the normal individual. Because the albumin sample was below the specimen value, the numerical results could not be obtained on biochemical examinations. We interpret all these results as making DMSO a caretaking aid. Since each one was not enough alone we used 3 parameters and the results were positive when we refer to the values of a normal healthy individual in parallel. We hope to extend the study further by adding new parameters and genetic analyzes, by increasing the number of samples, and by using DMSO as an adjunct agent in the treatment of liver cancer.

Keywords: hepatocellular carcinoma, HepG2, dimethyl sulfoxide, cell culture, ELISA

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220 The City Narrated from the Hill, Evaluation of Natural Fabric in Urban Plans: A Case Study of Santiago de Chile

Authors: Monica Sanchez

Abstract:

What responsibility does urban planning have on climate changes? How does the territory give us answers of resilience? Historically, urban plans have civilized territories: waters are channeled, grounds are sealed, foreign species are incorporated, native ones are extinguished, and/or enclosed spaces are heated or cooled. Socially this facilitates coexistence, but in turn brings negative environmental consequences. The past fifty years, mankind has tried to redirect these consequences through different strategies. Research studies produced strategies designed to alleviate climate change. Exploring the nature of territories has been incorporated in urban planning to discover natures response. The case to be studied is Santiago, Chile: for its combined impacts of climate change and the significant response by this city on climate governance in the last decades. Warmer areas in Santiago are seen in the areas of high-density buildings such as the commune of Recoleta, while the coldest are characterized by the predominance of low residential densities as the commune of Providencia. These two communes are separated and complemented by an undulating body that comes from the Andes mountains called San Cristobal Hill. What if the hill were taken into account when making roads, zoning and buildings? Was it difficult to prolong in the urban plans the hill characteristics to the city solving the intersection with other natural areas? Apparently it was, because the projected-profile informs us that the planned strategies used correspond to the same operations used in the flat areas of Santiago. This research focuses on: explaining the geographic relationships between city-hill; explaining the planning process around the hill with a morphological analysis; evaluating how the hill has been considered the in the city in the plans that intended to cushion the environmental impacts and studying what is missing on the hill and city to strengthen their integration. Therefore, the research will have different scales of understanding: addressing territorial scale -understanding the vegetation, topography and hydrology; a city scale -analyzing urban plans that Santiago has dealt with the environment and city; and a local scale -studying the integration and public spaces and coverage- norms of the adjacent communes. The expected outcome is to decipher possible deficits and capabilities of the current urban plans for climate change. It is anticipated that the hill and valley is now trying to reconcile after such a long separation. Yet it seems that never will prevail all the Rules of Nature, but the Urban Rules. The plans will require pruning, irrigation, control of invasive alien species and public safety standards, but will be rejoining a dose of nature with the building environment -this will protect us better from it from the time that we feared from it and knew little about it. Today we know a little more, enough to adapt to the process. Although nature is not perceived and we ignore it, it has a remarkable ability to respond.

Keywords: resilience, climate change, urban plans, land use, hills and cities, heat islands, morphology

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219 A System for Preventing Inadvertent Exposition of Staff Present outside the Operating Theater: Description and Clinical Test

Authors: Aya Al Masri, Kamel Guerchouche, Youssef Laynaoui, Safoin Aktaou, Malorie Martin, Fouad Maaloul

Abstract:

Introduction: Mobile C-arms move throughout operating rooms of the operating theater. Being designed to move between rooms, they are not equipped with relays to retrieve the exposition information and export it outside the room. Therefore, no light signaling is available outside the room to warn the X-ray emission for staff. Inadvertent exposition of staff outside the operating theater is a real problem for radiation protection. The French standard NFC 15-160 require that: (1) access to any room containing an X-ray emitting device must be controlled by a light signage so that it cannot be inadvertently crossed, and (2) setting up an emergency button to stop the X-ray emission. This study presents a system that we developed to meet these requirements and the results of its clinical test. Materials and methods: The system is composed of two communicating boxes: o The "DetectBox" is to be installed inside the operating theater. It identifies the various operation states of the C-arm by analyzing its power supply signal. The DetectBox communicates (in wireless mode) with the second box (AlertBox). o The "AlertBox" can operate in socket or battery mode and is to be installed outside the operating theater. It detects and reports the state of the C-arm by emitting a real time light signal. This latter can have three different colors: red when the C-arm is emitting X-rays, orange when it is powered on but does not emit X-rays, and green when it is powered off. The two boxes communicate on a radiofrequency link exclusively carried out in the ‘Industrial, Scientific and Medical (ISM)’ frequency bands and allows the coexistence of several on-site warning systems without communication conflicts (interference). Taking into account the complexity of performing electrical works in the operating theater (for reasons of hygiene and continuity of medical care), this system (having a size <10 cm²) works in complete safety without any intrusion in the mobile C-arm and does not require specific electrical installation work. The system is equipped with emergency button that stops X-ray emission. The system has been clinically tested. Results: The clinical test of the system shows that: it detects X-rays having both high and low energy (50 – 150 kVp), high and low photon flow (0.5 – 200 mA: even when emitted for a very short time (<1 ms)), Probability of false detection < 10-5, it operates under all acquisition modes (continuous, pulsed, fluoroscopy mode, image mode, subtraction and movie mode), it is compatible with all C-arm models and brands. We have also tested the communication between the two boxes (DetectBox and AlertBox) in several conditions: (1) Unleaded room, (2) leaded room, and (3) rooms with particular configuration (sas, great distances, concrete walls, 3 mm of lead). The result of these last tests was positive. Conclusion: This system is a reliable tool to alert the staff present outside the operating room for X-ray emission and insure their radiation protection.

Keywords: Clinical test, Inadvertent staff exposition, Light signage, Operating theater

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218 QIP: Introducing a Dedicated Ozurdex Clinic

Authors: Vaisnavy Govindasamy, Saba Ishrat

Abstract:

Introduction: The Dexamethasone Intravitreal Implant 0.7 mg (OzurdexTM, Allergan®) is a biodegradable corticosteroid implant approved by the FDA for managing diabetic macular edema (DMO), macular edema following branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO), and posterior segment non-infectious uveitis. This implant can release dexamethasone over a six-month period, exhibiting peak effectiveness between 60 and 90 days post-administration. The intravitreal injection should be performed under sterile conditions. At James Cook University Hospital (JCUH), Ozurdex injections are currently administered in the Vitreo-Retinal (VR) theatre. This study aimed to evaluate the feasibility and potential advantages of establishing a dedicated clinic for Ozurdex administration separate from the VR theatre setting. Method: Retrospectively, data of all Ozurdex injections administered between October 2021 to October 2022 was collected from operating theatre registers at JCUH. Data pertaining to the indications for Ozurdex; waiting times from referral date to date of injection; duration of theatre time consumed; and post-injection complications were collected from electronic notes. The resources needed to establish a dedicated Ozurdex clinic were evaluated. Over a six-month period from October 2023 to March 2024, we gathered data on utilization of theatre 28. Results: A total of 135 Ozurdex injections were administered. Among the indications, uveitis represented 47.3% of cases, DMO with 23.6% and RVO with 22.9%. Remaining cases lacked sufficient data. Each Ozurdex injection procedure consumed 15 minutes in the VR theatre list. Complications arose in 5% of injections, totaling 7 cases. These included glaucoma, ocular hypertension, subconjunctival haemorrhage and implant migration. Waiting times averaged 6 weeks from date for referral to procedure date. We also found that, on an average theatre 28 was offered but remained unused for 4 days, totalling eight sessions in a month. Analysis: Establishing a sperate Ozurdex clinic would improve the quality of patient care in following ways: 1.Decrease injection waiting times (currently averaging 6 weeks), leading to better visual outcomes. 2.Free up approximately three hours of theatre time in Vitreo-Retina theatres each month, allowing for 3-4 additional surgeries. Reduce waiting times for critical retinal surgeries and enhance visual outcomes. 3.Provide additional training opportunities for trainees and retina fellows, improving their skills. 4.Optimize the use of empty theatre slots (theatre 28) currently experiencing underutilization of resources. Conclusion: These findings support the implementation of a separate clinic for administering Ozurdex injections at JCUH. It is evident that introducing a dedicated clinic will enhance operational efficiency, optimise resource utilsation, and improve overall quality of care for patients undergoing this treatment.

Keywords: opthalmology, ozurdex, efficiency, complication

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217 Comparison of Nutritional Status of Asthmatic vs Non-asthmatic Adults

Authors: Ayesha Mushtaq

Abstract:

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

Keywords: NUTRI, BMI, asthma, food

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216 A Cross-Sectional Study Assessing Communication Practices among Doctors at a University Hospital in Pakistan

Authors: Muhammad Waqas Baqai, Noman Shahzad, Rehman Alvi

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Communication among health care givers is the essence of quality patient care and any compromise results in errors and inefficiency leading to cumbersome outcomes. The use of smartphone among health professionals has increased tremendously. Almost every health professional carries it and majority of them uses a third party communication software called whatsApp for work related communications. It gives instant access to the person responsible for any particular query and therefore helps in efficient and timely decision making. It is also an easy way of sharing medical documents, multimedia and provides platform for consensual decision making through group discussions. However clinical communication through whatsApp has some demerits too including reduction in verbal communication, worsening professional relations, unprofessional behavior, risk of confidentiality breach and threats from cyber-attacks. On the other hand the traditional pager device being used in many health care systems is a unidirectional communication that lacks the ability to convey any information other than the number to which the receiver has to respond. Our study focused on these two widely used modalities of communication among doctors of the largest tertiary care center of Pakistan i.e. The Aga Khan University Hospital. Our aim was to note which modality is considered better and has fewer threats to medical data. Approval from ethical review committee of the institute was taken prior to conduction of this study. We submitted an online survey form to all the interns and residents working at our institute and collected their response in a month’s time. 162 submissions were recorded and analyzed using descriptive statistics. Only 20% of them were comfortable with using pagers exclusively, 52% with whatsApp and 28% with both. 65% think that whatsApp is time-saving and quicker than pager. 54% of them considered whatsApp to be causing nuisance from work related notifications in their off-work hours. 60% think that they are more likely to miss information through pager system because of the unidirectional nature. Almost all (96%) of residents and interns found whatsApp to be useful in terms of saving information for future reference. For urgent issues, majority (70%) preferred pager over whatsApp and also pager was considered more valid in terms of hospital policies and legal issues. Among major advantages of whatsApp as listed by them were; easy mass communication, sharing of clinical pictures, universal access and no need of carrying additional device. However the major drawback of using whatsApp for clinical communication that everyone shared was threat to patients’ confidentiality as clinicians usually share pictures of wounds, clinical documents etc. Lastly we asked them if they think there is a need of a separate application for instant communication dedicated to clinical communication only and 90% responded positively. Therefore, we concluded that both modalities have their merits and demerits but the greatest drawback with whatsApp is the risk of breach in patients’ confidentiality and off-work disturbance. Hence, we recommend a more secure, institute-run application for all intra hospital communications where they can share documents, pictures etc. easily under a controlled environment.

Keywords: WhatsApp, pager, clinical communication, confidentiality

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215 Molecular Detection and Antibiotics Resistance Pattern of Extended-Spectrum Beta-Lactamase Producing Escherichia coli in a Tertiary Hospital in Enugu, Nigeria

Authors: I. N. Nwafia, U. C. Ozumba, M. E. Ohanu, S. O. Ebede

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Antibiotic resistance is increasing globally and has become a major health challenge. Extended-spectrum beta-lactamase is clinically important because the ESBL gene are mostly plasmid encoded and these plasmids frequently carry genes encoding resistance to other classes of antimicrobials thereby limiting antibiotic options in the treatment of infections caused by these organisms. The specific objectives of this study were to determine the prevalence of ESBLs production in Escherichia coli, to determine the antibiotic susceptibility pattern of ESBLs producing Escherichia coli, to detect TEM, SHV and CTX-M genes and the risk factors to acquisition of ESBL producing Escherichia coli. The protocol of the study was approved by Health Research and Ethics committee of the University of Nigeria Teaching Hospital (UNTH), Enugu. It was a descriptive cross-sectional study that involved all hospitalized patients in UNTH from whose specimens Escherichia coli was isolated during the period of the study. The samples analysed were urine, wound swabs, blood and cerebrospinal fluid. These samples were cultured in 5% sheep Blood agar and MacConkey agar (Oxoid Laboratories, Cambridge UK) and incubated at 35-370C for 24 hours. Escherichia coli was identified with standard biochemical tests and confirmed using API 20E auxanogram (bioMerieux, Marcy 1'Etoile, France). The antibiotic susceptibility testing was done by disc diffusion method and interpreted according to the Clinical and Laboratory Standard Institute guideline. ESBL production was confirmed using ESBL Epsilometer test strips (Liofilchem srl, Italy). The ESBL bla genes were detected with polymerase chain reaction, after extraction of DNA with plasmid mini-prep kit (Jena Bioscience, Jena, Germany). Data analysis was with appropriate descriptive and inferential statistics. One hundred and six isolates (53.00%) out of the 200 were from urine, followed by isolates from different swabs specimens 53(26.50%) and the least number of the isolates 4(2.00) were from blood (P value = 0.096). Seventy (35.00%) out of the 200 isolates, were confirmed positive for ESBL production. Forty-two (60.00%) of the isolates were from female patients while 28(40.00%) were from male patients (P value = 0.13). Sixty-eight (97.14%) of the isolates were susceptible to imipenem while all of the isolates were resistant to ampicillin, chloramphenicol and tetracycline. From the 70 positive isolates the ESBL genes detected with polymerase chain reaction were blaCTX-M (n=26; 37.14%), blaTEM (n=7; 10.00%), blaSHV (n=2; 2.86%), blaCTX-M/TEM (n=7; 10.0%), blaCTX-M/SHV (n=14; 20.0%) and blaCTX-M/TEM/SHV (n=10; 14.29%). There was no gene detected in 4(5.71%) of the isolates. The most associated risk factors to infections caused by ESBL producing Escherichia coli was previous antibiotics use for the past 3 months followed by admission in the intensive care unit, recent surgery, and urinary catheterization. In conclusion, ESBLs was detected in 4 of every 10 Escherichia coli with the predominant gene detected being CTX-M. This knowledge will enable appropriate measures towards improvement of patient health care, antibiotic stewardship, research and infection control in the hospital.

Keywords: antimicrobial, Escherichia coli, extended spectrum beta lactamase, resistance

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214 Web-Based Instructional Program to Improve Professional Development: Recommendations and Standards for Radioactive Facilities in Brazil

Authors: Denise Levy, Gian M. A. A. Sordi

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This web based project focuses on continuing corporate education and improving workers' skills in Brazilian radioactive facilities throughout the country. The potential of Information and Communication Technologies (ICTs) shall contribute to improve the global communication in this very large country, where it is a strong challenge to ensure high quality professional information to as many people as possible. The main objective of this system is to provide Brazilian radioactive facilities a complete web-based repository - in Portuguese - for research, consultation and information, offering conditions for learning and improving professional and personal skills. UNIPRORAD is a web based system to offer unified programs and inter-related information about radiological protection programs. The content includes the best practices for radioactive facilities in order to meet both national standards and international recommendations published by different organizations over the past decades: International Commission on Radiological Protection (ICRP), International Atomic Energy Agency (IAEA) and National Nuclear Energy Commission (CNEN). The website counts on concepts, definitions and theory about optimization and ionizing radiation monitoring procedures. Moreover, the content presents further discussions related to some national and international recommendations, such as potential exposure, which is currently one of the most important research fields in radiological protection. Only two publications of ICRP develop expressively the issue and there is still a lack of knowledge of fail probabilities, for there are still uncertainties to find effective paths to quantify probabilistically the occurrence of potential exposures and the probabilities to reach a certain level of dose. To respond to this challenge, this project discusses and introduces potential exposures in a more quantitative way than national and international recommendations. Articulating ICRP and AIEA valid recommendations and official reports, in addition to scientific papers published in major international congresses, the website discusses and suggests a number of effective actions towards safety which can be incorporated into labor practice. The WEB platform was created according to corporate public needs, taking into account the development of a robust but flexible system, which can be easily adapted to future demands. ICTs provide a vast array of new communication capabilities and allow to spread information to as many people as possible at low costs and high quality communication. This initiative shall provide opportunities for employees to increase professional skills, stimulating development in this large country where it is an enormous challenge to ensure effective and updated information to geographically distant facilities, minimizing costs and optimizing results.

Keywords: distance learning, information and communication technology, nuclear science, radioactive facilities

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213 Formulation of Lipid-Based Tableted Spray-Congealed Microparticles for Zero Order Release of Vildagliptin

Authors: Hend Ben Tkhayat , Khaled Al Zahabi, Husam Younes

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Introduction: Vildagliptin (VG), a dipeptidyl peptidase-4 inhibitor (DPP-4), was proven to be an active agent for the treatment of type 2 diabetes. VG works by enhancing and prolonging the activity of incretins which improves insulin secretion and decreases glucagon release, therefore lowering blood glucose level. It is usually used with various classes, such as insulin sensitizers or metformin. VG is currently only marketed as an immediate-release tablet that is administered twice daily. In this project, we aim to formulate an extended-release with a zero-order profile tableted lipid microparticles of VG that could be administered once daily ensuring the patient’s convenience. Method: The spray-congealing technique was used to prepare VG microparticles. Compritol® was heated at 10 oC above its melting point and VG was dispersed in the molten carrier using a homogenizer (IKA T25- USA) set at 13000 rpm. VG dispersed in the molten Compritol® was added dropwise to the molten Gelucire® 50/13 and PEG® (400, 6000, and 35000) in different ratios under manual stirring. The molten mixture was homogenized and Carbomer® amount was added. The melt was pumped through the two-fluid nozzle of the Buchi® Spray-Congealer (Buchi B-290, Switzerland) using a Pump drive (Master flex, USA) connected to a silicone tubing wrapped with silicone heating tape heated at the same temperature of the pumped mix. The physicochemical properties of the produced VG-loaded microparticles were characterized using Mastersizer, Scanning Electron Microscope (SEM), Differential Scanning Calorimeter (DSC) and X‐Ray Diffractometer (XRD). VG microparticles were then pressed into tablets using a single punch tablet machine (YDP-12, Minhua pharmaceutical Co. China) and in vitro dissolution study was investigated using Agilent Dissolution Tester (Agilent, USA). The dissolution test was carried out at 37±0.5 °C for 24 hours in three different dissolution media and time phases. The quantitative analysis of VG in samples was realized using a validated High-Pressure Liquid Chromatography (HPLC-UV) method. Results: The microparticles were spherical in shape with narrow distribution and smooth surface. DSC and XRD analyses confirmed the crystallinity of VG that was lost after being incorporated into the amorphous polymers. The total yields of the different formulas were between 70% and 80%. The VG content in the microparticles was found to be between 99% and 106%. The in vitro dissolution study showed that VG was released from the tableted particles in a controlled fashion. The adjustment of the hydrophilic/hydrophobic ratio of excipients, their concentration and the molecular weight of the used carriers resulted in tablets with zero-order kinetics. The Gelucire 50/13®, a hydrophilic polymer was characterized by a time-dependent profile with an important burst effect that was decreased by adding Compritol® as a lipophilic carrier to retard the release of VG which is highly soluble in water. PEG® (400,6000 and 35 000) were used for their gelling effect that led to a constant rate delivery and achieving a zero-order profile. Conclusion: Tableted spray-congealed lipid microparticles for extended-release of VG were successfully prepared and a zero-order profile was achieved.

Keywords: vildagliptin, spray congealing, microparticles, controlled release

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212 Effect of Ion Irradiation on the Microstructure and Properties of Chromium Coatings on Zircaloy-4 Substrate

Authors: Alexia Wu, Joel Ribis, Jean-Christophe Brachet, Emmanuel Clouet, Benoit Arnal, Elodie Rouesne, Stéphane Urvoy, Justine Roubaud, Yves Serruys, Frederic Lepretre

Abstract:

To enhance the safety of Light Water Reactor, accident tolerant fuel (ATF) claddings materials are under development. In the framework of CEA-AREVA-EDF collaborative program on ATF cladding materials, CEA has engaged specific studies on chromium coated zirconium alloys. Especially for Loss-of-Coolant-Accident situations, chromium coated claddings have shown some additional 'coping' time before achieving full embrittlement of the oxidized cladding, when compared to uncoated references – both tested in steam environment up to 1300°C. Nevertheless, the behavior of chromium coatings and the stability of the Zr-Cr interface under neutron irradiation remain unknown. Two main points are addressed: 1. Bulk Cr behavior under irradiation: Due to its BCC crystallographic structure, Cr is prone to Ductile-to-Brittle-Transition at quite high temperature. Irradiation could be responsible for a significant additional DBTT shift towards higher temperatures. 2. Zircaloy/Cr interface behavior under irradiation: Preliminary TEM examinations of un-irradiated samples revealed a singular Zircaloy-4/Cr interface with nanometric intermetallic phase layers. Such particular interfaces highlight questions of how they would behave under irradiation - intermetallic zirconium phases are known to be more or less stable under irradiations. Another concern is a potential enhancement of chromium diffusion into the zirconium-alpha based substrate. The purpose of this study is then to determine the behavior of such coatings after ion irradiations, as a surrogate to neutron irradiation. Ion irradiations were performed at the Jannus-Saclay facility (France). 20 MeV Kr8+ ions at 400°C with a flux of 2.8x1011 ions.cm-2.s-1 were used to irradiate chromium coatings of 1-2 µm thick on Zircaloy-4 sheets substrate. At the interface, the calculated damage is close to 10 dpa (SRIM, Quick Calculation Damage mode). Thin foil samples were prepared with FIB for both as-received and irradiated coated samples. Transmission Electron Microscopy (TEM) and in-situ tensile tests in a Scanning Electron Microscope are being used to characterize the un-irradiated and irradiated materials. High Resolution TEM highlights a great complexity of the interface before irradiation since it is formed of an alternation of intermetallic phases – C14 and C15. The interfaces formed by these intermetallic phases with chromium and zirconium show semi-coherency. Chemical analysis performed before irradiation shows some iron enrichment at the interface. The chromium coating bulk microstructures and properties are also studied before and after irradiation. On-going in-situ tensile tests focus on the capacity of chromium coatings to sustain some plastic deformation when tested up to 350°C. The stability of the Cr/Zr interface is shown after ion irradiation up to 10 dpa. This observation constitutes the first result after irradiation on these new coated claddings materials.

Keywords: accident tolerant fuel, HRTEM, interface, ion-irradiation

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211 Tuberculous Osteomyelitis Mimicking Tumours and Tumour-Like Lesions of Bone: Clinico-Radiologic Study of 22 Patients

Authors: Parveen Kundu, Zile Singh, Kunika Kundu, Swaran Kaur

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Context: Tuberculous osteomyelitis is a relatively uncommon condition that can present with various clinical and radiological features, often mimicking bone tumors or tumor-like lesions. In endemic countries like India, tuberculosis should be considered as a potential differential diagnosis for lytic bone lesions. This study aimed to highlight the different presentations of tuberculosis that can mimic tumors or tumor-like lesions in bone and emphasize the successful outcome of antitubercular therapy (ATT) in treating these cases. Research Aim: The main objective of this research was to explore the varied presentations of tuberculosis that mimic bone tumors or tumor-like lesions both clinically and radiologically, focusing on different bones. The study aimed to raise awareness among clinicians about this possibility and highlight the importance of histopathological confirmation before initiating treatment for lytic bone lesions. Methodology: This study utilized a retrospective review of 22 patients with suspected lytic bone lesions, who were subsequently diagnosed with tuberculous osteomyelitis through histopathological examination. The cases were collected over a period of ten years. Eleven cases required curettage for extensive lesions with sequestrations, while all 22 patients received 12 months of antitubercular therapy. Findings: The study included 14 male and 8 female patients, ranging in age from 3 to 61 years, with an average age of 22.05. The clinical and radiological presentations varied, with examples including bone cysts in the metaphyseal area of long bones, lesions resembling chondroblastomas, giant cell tumors, and osteoid osteoma, as well as multifocal lytic lesions resembling metastasis or multiple myeloma. One patient had lesions in both the clavicle and hand. Lesions mimicking chondromas were also observed in the phalanges of the hand and foot metatarsal. All patients showed resolution of the lesions and no residual disability following ATT. Theoretical Importance: This study highlights the importance of considering tuberculosis as a potential differential diagnosis for lytic bone lesions, particularly in endemic regions. It emphasizes the need for histopathological confirmation to accurately diagnose tuberculous osteomyelitis, as this is considered the gold standard. Data Collection and Analysis Procedures: Data for this study were collected retrospectively from medical records and radiological images of the 22 patients. The cases were analyzed based on clinical presentation, radiological findings, and histopathological confirmation. The outcomes of antitubercular therapy were also assessed. The data were summarized and presented descriptively. Question Addressed: This study aimed to address the question of how tuberculosis can mimic different bone tumors and tumor-like lesions clinically and radiologically. It also aimed to assess the successful outcome of antitubercular therapy in treating these cases. Conclusion: Tuberculous osteomyelitis can present with varied clinical and radiological features, often mimicking bone tumors or tumor-like lesions. Clinicians should consider tuberculosis as a potential diagnosis for lytic bone lesions, especially in endemic areas. Histopathological confirmation is essential for accurate diagnosis. Antitubercular therapy is an effective treatment for tuberculous osteomyelitis, leading to the resolution of the lesions with no residual disability.

Keywords: tuberculosis, tumor, curettage, bone

Procedia PDF Downloads 91
210 Effect of Renin Angiotensin Pathway Inhibition on the Efficacy of Anti-programmed Cell Death (PD-1/L-1) Inhibitors in Advanced Non-small Cell Lung Cancer Patients- Comparison of Single Hospital Retrospective Assessment to the Published Literature

Authors: Esther Friedlander, Philip Friedlander

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The use of immunotherapy that inhibits programmed death-1 (PD-1) or its ligand PD-L1 confers survival benefits in patients with non-small cell lung cancer (NSCLC). However, approximately 45% of patients experience primary treatment resistance, necessitating the development of strategies to improve efficacy. While the renin-angiotensin system (RAS) has systemic hemodynamic effects, tissue-specific regulation exists along with modulation of immune activity in part through regulation of myeloid cell activity, leading to the hypothesis that RAS inhibition may improve anti-PD-1/L-1 efficacy. A retrospective analysis was conducted that included 173 advanced solid tumor cancer patients treated at Valley Hospital, a community Hospital in New Jersey, USA, who were treated with a PD-1/L-1 inhibitor in a defined time period showing a statistically significant relationship between RAS pathway inhibition (RASi through concomitant treatment with an ACE inhibitor or angiotensin receptor blocker) and positive efficacy to the immunotherapy that was independent of age, gender and cancer type. Subset analysis revealed strong numerical benefit for efficacy in both patients with squamous and nonsquamous NSCLC as determined by documented clinician assessment of efficacy and by duration of therapy. A PUBMED literature search was now conducted to identify studies assessing the effect of RAS pathway inhibition on anti-PD-1/L1 efficacy in advanced solid tumor patients and compare these findings to those seen in the Valley Hospital retrospective study with a focus on NSCLC specifically. A total of 11 articles were identified assessing the effects of RAS pathway inhibition on the efficacy of checkpoint inhibitor immunotherapy in advanced cancer patients. Of the 11 studies, 10 assessed the effect on survival of RASi in the context of treatment with anti-PD-1/PD-L1, while one assessed the effect on CTLA-4 inhibition. Eight of the studies included patients with NSCLC, while the remaining 2 were specific to genitourinary malignancies. Of the 8 studies, two were specific to NSCLC patients, with the remaining 6 studies including a range of cancer types, of which NSCLC was one. Of these 6 studies, only 2 reported specific survival data for the NSCLC subpopulation. Patient characteristics, multivariate analysis data and efficacy data seen in the 2 NSLCLC specific studies and in the 2 basket studies, which provided data on the NSCLC subpopulation, were compared to that seen in the Valley Hospital retrospective study supporting a broader effect of RASi on anti-PD-1/L1 efficacy in advanced NSLCLC with the majority of studies showing statistically significant benefit or strong statistical trends but with one study demonstrating worsened outcomes. This comparison of studies extends published findings to the community hospital setting and supports prospective assessment through randomized clinical trials of efficacy in NSCLC patients with pharmacodynamic components to determine the effect on immune cell activity in tumors and on the composition of the tumor microenvironment.

Keywords: immunotherapy, cancer, angiotensin, efficacy, PD-1, lung cancer, NSCLC

Procedia PDF Downloads 69
209 Implementation of Performance Management and Development System: The Case of the Eastern Cape Provincial Department of Health, South Africa

Authors: Thanduxolo Elford Fana

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Rationale and Purpose: Performance management and development system are central to effective and efficient service delivery, especially in highly labour intensive sectors such as South African public health. Performance management and development systems seek to ensure that good employee performance is rewarded accordingly, while those who underperform are developed so that they can reach their full potential. An effective and efficiently implemented performance management system motivates and improves employee engagement. The purpose of this study is to examine the implementation of the performance management and development system and the challenges that are encountered during its implementation in the Eastern Cape Provincial Department of Health. Methods: A qualitative research approach and a case study design was adopted in this study. The primary data were collected through observations, focus group discussions with employees, a group interview with shop stewards, and in-depth interviews with supervisors and managers, from April 2019 to September 2019. There were 45 study participants. In-depth interviews were held with 10 managers at facility level, which included chief executive officer, chief medical officer, assistant director’s in human resources management, patient admin, operations, finance, and two area manager and two operation managers nursing. A group interview was conducted with five shop stewards and an in-depth interview with one shop steward from the group. Five focus group discussions were conducted with clinical and non-clinical staff. The focus group discussions were supplemented with an in-depth interview with one person from each group in order to counter the group effect. Observations included moderation committee, contracting, and assessment meetings. Findings: The study shows that the performance management and development system was not properly implemented. There was non-compliance to performance management and development system policy guidelines in terms of time lines for contracting, evaluation, payment of incentives to good performers, and management of poor performance. The study revealed that the system is ineffective in raising the performance of employees and unable to assist employees to grow. The performance bonuses were no longer paid to qualifying employees. The study also revealed that lack of capacity and commitment, poor communication, constant policy changes, financial constraints, weak and highly bureaucratic management structures, union interference were challenges that were encountered during the implementation of the performance management and development system. Lastly, employees and supervisors were rating themselves three irrespective of how well or bad they performed. Conclusion: Performance management is regarded as vital to improved performance of the health workforce and healthcare service delivery among populations. Effective implementation of performance management and development system depends on well-capacitated and unbiased management at facility levels. Therefore, there is an urgent need to improve communication, link performance management to rewards, and capacitate staff on performance management and development system, as it is key to improved public health sector outcomes or performance.

Keywords: challenges, implementation, performance management and development system, public hospital

Procedia PDF Downloads 139
208 Antimicrobial Efficacy of Some Antibiotics Combinations Tested against Some Molecular Characterized Multiresistant Staphylococcus Clinical Isolates, in Egypt

Authors: Nourhan Hussein Fanaki, Hoda Mohamed Gamal El-Din Omar, Nihal Kadry Moussa, Eva Adel Edward Farid

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The resistance of staphylococci to various antibiotics has become a major concern for health care professionals. The efficacy of the combinations of selected glycopeptides (vancomycin and teicoplanin) with gentamicin or rifampicin, as well as that of gentamicin/rifampicin combination, was studied against selected pathogenic staphylococcus isolated from Egypt. The molecular distribution of genes conferring resistance to these four antibiotics was detected among tested clinical isolates. Antibiotic combinations were studied using the checkerboard technique and the time-kill assay (in both the stationary and log phases). Induction of resistance to glycopeptides in staphylococci was tried in the absence and presence of diclofenac sodium as inducer. Transmission electron microscopy was used to study the effect of glycopeptides on the ultrastructure of the cell wall of staphylococci. Attempts were made to cure gentamicin resistance plasmids and to study the transfer of these plasmids by conjugation. Trials for the transformation of the successfully isolated gentamicin resistance plasmid to competent cells were carried out. The detection of genes conferring resistance to the tested antibiotics was performed using the polymerase chain reaction. The studied antibiotic combinations proved their efficacy, especially when tested during the log phase. Induction of resistance to glycopeptides in staphylococci was more promising in presence of diclofenac sodium, compared to its absence. Transmission electron microscopy revealed the thickening of bacterial cell wall in staphylococcus clinical isolates due to the presence of tested glycopeptides. Curing of gentamicin resistance plasmids was only successful in 2 out of 9 tested isolates, with a curing rate of 1 percent for each. Both isolates, when used as donors in conjugation experiments, yielded promising conjugation frequencies ranging between 5.4 X 10-2 and 7.48 X 10-2 colony forming unit/donor cells. Plasmid isolation was only successful in one out of the two tested isolates. However, low transformation efficiency (59.7 transformants/microgram plasmid DNA) of such plasmids was obtained. Negative regulators of autolysis, such as arlR, lytR and lrgB, as well as cell-wall associated genes, such as pbp4 and/or pbp2, were detected in staphylococcus isolates with reduced susceptibility to the tested glycopeptides. Concerning rifampicin resistance genes, rpoBstaph was detected in 75 percent of the tested staphylococcus isolates. It could be concluded that in vitro studies emphasized the usefulness of the combination of vancomycin or teicoplanin with gentamicin or rifampicin, as well as that of gentamicin with rifampicin, against staphylococci showing varying resistance patterns. However, further in vivo studies are required to ensure the safety and efficacy of such combinations. Diclofenac sodium can act as an inducer of resistance to glycopeptides in staphylococci. Cell-wall thickness is a major contributor to such resistance among them. Gentamicin resistance in these strains could be chromosomally or plasmid mediated. Multiple mutations in the rpoB gene could mediate staphylococcus resistance to rifampicin.

Keywords: glycopeptides, combinations, induction, diclofenac, transmission electron microscopy, polymerase chain reaction

Procedia PDF Downloads 294
207 Comparative Study of Outcome of Patients with Wilms Tumor Treated with Upfront Chemotherapy and Upfront Surgery in Alexandria University Hospitals

Authors: Golson Mohamed, Yasmine Gamasy, Khaled EL-Khatib, Anas Al-Natour, Shady Fadel, Haytham Rashwan, Haytham Badawy, Nadia Farghaly

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Introduction: Wilm's tumor is the most common malignant renal tumor in children. Much progress has been made in the management of patients with this malignancy over the last 3 decades. Today treatments are based on several trials and studies conducted by the International Society of Pediatric Oncology (SIOP) in Europe and National Wilm's Tumor Study Group (NWTS) in the USA. It is necessary for us to understand why do we follow either of the protocols, NWTS which follows the upfront surgery principle or the SIOP which follows the upfront chemotherapy principle in all stages of the disease. Objective: The aim of is to assess outcome in patients treated with preoperative chemotherapy and patients treated with upfront surgery to compare their effect on overall survival. Study design: to decide which protocol to follow, study was carried out on records for patients aged 1 day to 18 years old suffering from Wilm's tumor who were admitted to Alexandria University Hospital, pediatric oncology, pediatric urology and pediatric surgery departments, with a retrospective survey records from 2010 to 2015, Design and editing of the transfer sheet with a (PRISMA flow study) Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Data were fed to the computer and analyzed using IBM SPSS software package version 20.0. (11) Qualitative data were described using number and percent. Quantitative data were described using Range (minimum and maximum), mean, standard deviation and median. Comparison between different groups regarding categorical variables was tested using Chi-square test. When more than 20% of the cells have expected count less than 5, correction for chi-square was conducted using Fisher’s Exact test or Monte Carlo correction. The distributions of quantitative variables were tested for normality using Kolmogorov-Smirnov test, Shapiro-Wilk test, and D'Agstino test, if it reveals normal data distribution, parametric tests were applied. If the data were abnormally distributed, non-parametric tests were used. For normally distributed data, a comparison between two independent populations was done using independent t-test. For abnormally distributed data, comparison between two independent populations was done using Mann-Whitney test. Significance of the obtained results was judged at the 5% level. Results: A significantly statistical difference was observed for survival between the two studied groups favoring the upfront chemotherapy(86.4%)as compared to the upfront surgery group (59.3%) where P=0.009. As regard complication, 20 cases (74.1%) out of 27 were complicated in the group of patients treated with upfront surgery. Meanwhile, 30 cases (68.2%) out of 44 had complications in patients treated with upfront chemotherapy. Also, the incidence of intraoperative complication (rupture) was less in upfront chemotherapy group as compared to upfront surgery group. Conclusion: Upfront chemotherapy has superiority over upfront surgery.As the patient who started with upfront chemotherapy shown, higher survival rate, less percent in complication, less percent needed for radiotherapy, and less rate in recurrence.

Keywords: Wilm's tumor, renal tumor, chemotherapy, surgery

Procedia PDF Downloads 318
206 Genetic Polymorphism and Insilico Study Epitope Block 2 MSP1 Gene of Plasmodium falciparum Isolate Endemic Jayapura

Authors: Arsyam Mawardi, Sony Suhandono, Azzania Fibriani, Fifi Fitriyah Masduki

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Malaria is an infectious disease caused by Plasmodium sp. This disease has a high prevalence in Indonesia, especially in Jayapura. The vaccine that is currently being developed has not been effective in overcoming malaria. This is due to the high polymorphism in the Plasmodium genome especially in areas that encode Plasmodium surface proteins. Merozoite Surface Protein 1 (MSP1) Plasmodium falciparum is a surface protein that plays a role in the invasion process in human erythrocytes through the interaction of Glycophorin A protein receptors and sialic acid in erythrocytes with Reticulocyte Binding Proteins (RBP) and Duffy Adhesion Protein (DAP) ligands in merozoites. MSP1 can be targeted to be a specific antigen and predicted epitope area which will be used for the development of diagnostic and malaria vaccine therapy. MSP1 consists of 17 blocks, each block is dimorphic, and has been marked as the K1 and MAD20 alleles. Exceptions only in block 2, because it has 3 alleles, among others K1, MAD20 and RO33. These polymorphisms cause allelic variations and implicate the severity of patients infected P. falciparum. In addition, polymorphism of MSP1 in Jayapura isolates has not been reported so it is interesting to be further identified and projected as a specific antigen. Therefore, in this study, we analyzed the allele polymorphism as well as detected the MSP1 epitope antigen candidate on block 2 P. falciparum. Clinical samples of selected malaria patients followed the consecutive sampling method, examining malaria parasites with blood preparations on glass objects observed through a microscope. Plasmodium DNA was isolated from the blood of malarial positive patients. The block 2 MSP1 gene was amplified using PCR method and cloned using the pGEM-T easy vector then transformed to TOP'10 E.coli. Positive colonies selection was performed with blue-white screening. The existence of target DNA was confirmed by PCR colonies and DNA sequencing methods. Furthermore, DNA sequence analysis was done through alignment and formation of a phylogenetic tree using MEGA 6 software and insilico analysis using IEDB software to predict epitope candidate for P. falciparum. A total of 15 patient samples have been isolated from Plasmodium DNA. PCR amplification results show the target gene size about ± 1049 bp. The results of MSP1 nucleotide alignment analysis reveal that block 2 MSP1 genes derived from the sample of malarial patients were distributed in four different allele family groups, K1 (7), MAD20 (1), RO33 (0) and MSP1_Jayapura (10) alleles. The most commonly appears of the detected allele is MSP1_Jayapura single allele. There was no significant association between sex variables, age, the density of parasitemia and alel variation (Mann Whitney, U > 0.05), while symptomatic signs have a significant difference as a trigger of detectable allele variation (U < 0.05). In this research, insilico study shows that there is a new epitope antigen candidate from the MSP1_Jayapura allele and it is predicted to be recognized by B cells with 17 amino acid lengths in the amino acid sequence 187 to 203.

Keywords: epitope candidate, insilico analysis, MSP1 P. falciparum, polymorphism

Procedia PDF Downloads 180
205 An Integrated Approach to Child Care Earthquake Preparedness through “Telemachus” Project

Authors: A. Kourou, S. Kyriakopoulos, N. Anyfanti

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A lot of children under the age of five spend their daytime hours away from their home, in a kindergarten. Caring for children is a serious subject, and their safety in case of earthquake is the first priority. Being aware of earthquakes helps to prioritize the needs and take the appropriate actions to limit the effects. Earthquakes occurring anywhere at any time require emergency planning. Earthquake planning is a cooperative effort and childcare providers have unique roles and responsibilities. Greece has high seismicity and Ionian Islands Region has the highest seismic activity of the country. The last five years Earthquake Planning and Protection Organization (EPPO), which is a national organization, has analyzed the needs and requirements of kindergartens on earthquake protection issues. In this framework it has been noticed that although the State requires child care centers to hold drills, the standards for emergency preparedness in these centers are varied, and a lot of them had not written plans for emergencies. For these reasons, EPPO supports the development of emergency planning guidance and familiarizes the day care centers’ staff being prepared for earthquakes. Furthermore, the Handbook on Day Care Earthquake Planning that has been developed by EPPO helps the providers to understand that emergency planning is essential to risk reduction. Preparedness and training should be ongoing processes, thus EPPO implements every year dozens of specific seminars on children’s disaster related needs. This research presents the results of a survey that detects the level of earthquake preparedness of kindergartens in all over the country and Ionian Islands too. A closed-form questionnaire of 20 main questions was developed for the survey in order to detect the aspects of participants concerning the earthquake preparedness actions at individual, family and day care environment level. 2668 questionnaires were gathered from March 2014 to May 2019, and analyzed by EPPO’s Department of Education. Moreover, this paper presents the EPPO’s educational activities targeted to the Ionian Islands Region that implemented in the framework of “Telemachus” Project. To provide safe environment for children to learn, and staff to work is the foremost goal of any State, community and kindergarten. This project is funded under the Priority Axis "Environmental Protection and Sustainable Development" of Operational Plan "Ionian Islands 2014-2020". It is increasingly accepted that emergency preparedness should be thought of as an ongoing process rather than a one-time activity. Creating an earthquake safe daycare environment that facilitates learning is a challenging task. Training, drills, and update of emergency plan should take place throughout the year at kindergartens to identify any gaps and to ensure the emergency procedures. EPPO will continue to work closely with regional and local authorities to actively address the needs of children and kindergartens before, during and after earthquakes.

Keywords: child care centers, education on earthquake, emergency planning, kindergartens, Ionian Islands Region of Greece

Procedia PDF Downloads 118
204 The Impact of Shifting Trading Pattern from Long-Haul to Short-Sea to the Car Carriers’ Freight Revenues

Authors: Tianyu Wang, Nikita Karandikar

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

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

Procedia PDF Downloads 121
203 Pharmacokinetic Assessment of Antimicrobial Treatment of Acute Exacerbations of Chronic Obstructive Pulmonary Disease in Hospitalized Patients Colonized with Pseudomonas aeruginosa

Authors: Juliette Begin, Juliano Colapelle, Andrea Taratanu, Daniel Thirion, Amelie Marsot, Bryan A. Ross

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Chronic obstructive pulmonary disease (COPD), a leading cause of death globally, is characterized by chronic airflow obstruction and acute exacerbations (AECOPDs) that are often triggered by respiratory infections. Pseudomonas aeruginosa (P. aeruginosa), a potentially serious bacterial cause of AECOPDs, is treated with targeted anti-pseudomonal antibiotics. These select few antimicrobials are often used as first-line therapy in patients who are clinically unwell and/or in those suspected of P. aeruginosa-related infection prior to confirmation, potentially contributing to antimicrobial resistance. The present study evaluates prescribing practices in patients with a confirmed sputum history of P. aeruginosa admitted for AECOPD at the McGill University Health Centre (MUHC) and treated with anti-pseudomonal antibiotics. Serum antibiotic concentrations were measured from the same-day peak, trough, and mid-dose blood sampling intervals after reaching steady-state (on or after day 3) and were quantified using ultra-high-performance liquid chromatography (UHPLC). Demographic, clinical, and treatment outcomes were extracted from patient medical charts. Treatment failure was defined by respiratory-related death or mechanical ventilation after ≥3 days of antibiotics; antibiotic therapy extended beyond 2 weeks or a new antibiotic regimen started; or urgent care readmission within 30 days for AECOPD. To date, 9 of 30 planned participants have completed testing: seven received ciprofloxacin, one received meropenem, and one received piperacillin-tazobactam. Due to serum sample batching requirements, the serum ciprofloxacin concentration results for the first 2/8 participants are presented at the time of writing. The first participant had serum levels of 5.45mg/L (T₀), 4.74mg/L (T₅₀), and 4.49mg/L (T₁₀₀), while the second had serum levels of 5mg/L (T₀), 2.6mg/L (T₅₀), and 2.51mg/L (T₁₀₀). Pharmacokinetic parameters Cmax (5.18±0.43mg/L), T₁/₂ (23.56±18.94hours), and AUC (181.9±155.95mg*h/l) were higher than reported monograph values and met target AUC-to-MIC ratio of >125. The patients treated with meropenem and with piperacillin-tazobactam experienced treatment failure. Preliminary results suggest that standard ciprofloxacin dosing in patients experiencing an AECOPD and colonized with P. aeruginosa appears to achieve effective serum concentrations. Final cohort results will inform the pharmacokinetic appropriateness and clinical sufficiency of current AECOPD antimicrobial strategies in P. aeruginosa-colonized patients. This study will guide clinicians in determining the appropriate dosing for AECOPD treatment to achieve therapeutic levels, optimizing outcomes, and minimizing adverse effects. It could also highlight the value of routine antibiotic level monitoring in patients with treatment failure to ensure optimal serum concentrations.

Keywords: acute exacerbation, antimicrobial resistance, chronic obstructive pulmonary disease, pharmacokinetics/pharmacodynamics, Pseudomonas aeruginosa

Procedia PDF Downloads 22
202 Inflation and Deflation of Aircraft's Tire with Intelligent Tire Pressure Regulation System

Authors: Masoud Mirzaee, Ghobad Behzadi Pour

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An aircraft tire is designed to tolerate extremely heavy loads for a short duration. The number of tires increases with the weight of the aircraft, as it is needed to be distributed more evenly. Generally, aircraft tires work at high pressure, up to 200 psi (14 bar; 1,400 kPa) for airliners and higher for business jets. Tire assemblies for most aircraft categories provide a recommendation of compressed nitrogen that supports the aircraft’s weight on the ground, including a mechanism for controlling the aircraft during taxi, takeoff; landing; and traction for braking. Accurate tire pressure is a key factor that enables tire assemblies to perform reliably under high static and dynamic loads. Concerning ambient temperature change, considering the condition in which the temperature between the origin and destination airport was different, tire pressure should be adjusted and inflated to the specified operating pressure at the colder airport. This adjustment superseding the normal tire over an inflation limit of 5 percent at constant ambient temperature is required because the inflation pressure remains constant to support the load of a specified aircraft configuration. On the other hand, without this adjustment, a tire assembly would be significantly under/over-inflated at the destination. Due to an increase of human errors in the aviation industry, exorbitant costs are imposed on the airlines for providing consumable parts such as aircraft tires. The existence of an intelligent system to adjust the aircraft tire pressure based on weight, load, temperature, and weather conditions of origin and destination airports, could have a significant effect on reducing the aircraft maintenance costs, aircraft fuel and further improving the environmental issues related to the air pollution. An intelligent tire pressure regulation system (ITPRS) contains a processing computer, a nitrogen bottle with 1800 psi, and distribution lines. Nitrogen bottle’s inlet and outlet valves are installed in the main wheel landing gear’s area and are connected through nitrogen lines to main wheels and nose wheels assy. Controlling and monitoring of nitrogen will be performed by a computer, which is adjusted according to the calculations of received parameters, including the temperature of origin and destination airport, the weight of cargo loads and passengers, fuel quantity, and wind direction. Correct tire inflation and deflation are essential in assuring that tires can withstand the centrifugal forces and heat of normal operations, with an adequate margin of safety for unusual operating conditions such as rejected takeoff and hard landings. ITPRS will increase the performance of the aircraft in all phases of takeoff, landing, and taxi. Moreover, this system will reduce human errors, consumption materials, and stresses imposed on the aircraft body.

Keywords: avionic system, improve efficiency, ITPRS, human error, reduced cost, tire pressure

Procedia PDF Downloads 250
201 Barriers and Facilitators of Implementing Digital Mental Health Resources in Underserved Regions of Ontario during the COVID-19 Pandemic

Authors: Samaneh Abedini, Diana Urajnik, Nicole Naccarato

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A high prevalence of mental health problems was observed in marginalized youth living in underserved regions of Ontario during the COVID-19 pandemic. To address this issue, a growing number of community-based traditional mental health services are offering digital mental health resources due to their accessibility, affordability, and scalability. The feasibility of providing these resources in underserved regions has been examined by researchers rather than by representatives of effective services within a mental health system. Indeed, digitalized mental health contents are not routinely embedded within local mental health organizations' services in Northern Ontario, where they can make a substantial impact. To date, many technology-based mental health initiatives have not been effectively implemented in this region. The obstacles associated with implementing digitalized mental health resources in Northern Ontario may be unique to that region. Thus, specific context-based considerations might need to be applied for developing and implementing digital resources by regional mental health organizations in Northern Ontario. The target population was child-serving organizations situated in northeastern Ontario, specifically within Greater Sudbury and the Sudbury District. A sample of six organizations were selected with representation from the mental health, social, and healthcare sectors. The project supervisor was in a unique position to access the organizations by virtue of existing relationships with the practice and lay communities at large. Thus, recruitment was conducted through professional outreach in partnership with the Center for Rural and Northern Health Research (CRaNHR). Semi-structured interviews were conducted with 1-2 key personnel (e.g., administrator, clinician) from participating organizations. Audio recordings from the semi-structured interviews were transcribed verbatim and thematically analyzed supported by NVivo. Thematic analysis of the data resulted in a total of 13 excerpts which were categorized into two major themes including 1) digital mental health services as a valuable resource for organizations both during and after the pandemic, and 2) barriers and facilitators to a successful implementation of digital mental health resources in northern Ontario. Four secondary themes were identified: 1) perceived barriers to implementation of digital mental health resources to the offered services by mental health agencies; 2) acceptability and feasibility of digital health sources for people living in northern Ontario; 3) data security, safety, and risk; and 4) connecting with clients. The employees of mental health organizations in northern Ontario considered digital mental health resources as generally acceptable to youth. However, they raised several concerns that may affect their implementation into routine practice and service delivery. The implementation of digital systems should be simple and straightforward and should enhance rather than hinder clinical workflows for staff. A clear plan for implementing technological services is also required for the successful adoption of digital systems. For successful adoption and implementation of digital systems, staff views must be considered.

Keywords: COVID-19 pandemic, digital mental health resources, Ontario, underserved

Procedia PDF Downloads 102
200 Achieving Sustainable Agriculture with Treated Municipal Wastewater

Authors: Reshu Yadav, Himanshu Joshi, S. K. Tripathi

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Fresh water is a scarce resource which is essential for humans and ecosystems, but its distribution is uneven. Agricultural production accounts for 70% of all surface water supplies. It is projected that against the expansion in the area equipped for irrigation by 0.6% per year, the global potential irrigation water demand would rise by 9.5% during 2021-25. This would, on one hand, have to compete against the sharply rising urban water demand. On the other, it would also have to face the fear of climate change, as temperatures rise and crop yields could drop from 10-30% in many large areas. The huge demand for irrigation combined with fresh water scarcity encourages to explore the reuse of wastewater as a resource. However, the use of such wastewater is often linked to the safety issues when used non judiciously or with poor safeguards while irrigating food crops. Paddy is one of the major crops globally and amongst the most important in South Asia and Africa. In many parts of the world, use of municipal wastewater has been promoted as a viable option in this regard. In developing and fast growing countries like India, regularly increasing wastewater generation rates may allow this option to be considered quite seriously. In view of this, a pilot field study was conducted at the Jagjeetpur Municipal Sewage treatment plant situated in the Haridwar town of Uttarakhand state, India. The objectives of the present study were to study the effect of treated wastewater on the production of various paddy varieties (Sharbati, PR-114, PB-1, Menaka, PB1121 and PB 1509) and emission of GHG gases (CO2, CH4 and N2O) as compared to the same varieties grown in the control plots irrigated with fresh water. Of late, the concept of water footprint assessment has emerged, which explains enumeration of various types of water footprints of an agricultural entity from its production to processing stages. Paddy, the most water demanding staple crop of Uttarakhand state, displayed a high green water footprint value of 2966.538 m3/ton. Most of the wastewater irrigated varieties displayed upto 6% increase in production, except Menaka and PB-1121, which showed a reduction in production (6% and 3% respectively), due to pest and insect infestation. The treated wastewater was observed to be rich in Nitrogen (55.94 mg/ml Nitrate), Phosphorus (54.24 mg/ml) and Potassium (9.78 mg/ml), thus rejuvenating the soil quality and not requiring any external nutritional supplements. Percentage increase of GHG gases on irrigation with treated municipal waste water as compared to control plots was observed as 0.4% - 8.6% (CH4), 1.1% - 9.2% (CO2), and 0.07% - 5.8% (N2O). The variety, Sharbati, displayed maximum production (5.5 ton/ha) and emerged as the most resistant variety against pests and insects. The emission values of CH4 ,CO2 and N2O were 729.31 mg/m2/d, 322.10 mg/m2/d and 400.21 mg/m2/d in water stagnant condition. This study highlighted a successful possibility of reuse of wastewater for non-potable purposes offering the potential for exploiting this resource that can replace or reduce existing use of fresh water sources in agricultural sector.

Keywords: greenhouse gases, nutrients, water footprint, wastewater irrigation

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199 Immunoliposome-Mediated Drug Delivery to Plasmodium-Infected and Non-Infected Red Blood Cells as a Dual Therapeutic/Prophylactic Antimalarial Strategy

Authors: Ernest Moles, Patricia Urbán, María Belén Jiménez-Díaz, Sara Viera-Morilla, Iñigo Angulo-Barturen, Maria Antònia Busquets, Xavier Fernàndez-Busquets

Abstract:

Bearing in mind the absence of an effective vaccine against malaria and its severe clinical manifestations causing nearly half a million deaths every year, this disease represents nowadays a major threat to life. Besides, the basic rationale followed by currently marketed antimalarial approaches is based on the administration of drugs on their own, promoting the emergence of drug-resistant parasites owing to the limitation in delivering drug payloads into the parasitized erythrocyte high enough to kill the intracellular pathogen while minimizing the risk of causing toxic side effects to the patient. Such dichotomy has been successfully addressed through the specific delivery of immunoliposome (iLP)-encapsulated antimalarials to Plasmodium falciparum-infected red blood cells (pRBCs). Unfortunately, this strategy has not progressed towards clinical applications, whereas in vitro assays rarely reach drug efficacy improvements above 10-fold. Here, we show that encapsulation efficiencies reaching >96% can be achieved for the weakly basic drugs chloroquine (CQ) and primaquine using the pH gradient active loading method in liposomes composed of neutrally charged, saturated phospholipids. Targeting antibodies are best conjugated through their primary amino groups, adjusting chemical crosslinker concentration to retain significant antigen recognition. Antigens from non-parasitized RBCs have also been considered as targets for the intracellular delivery of drugs not affecting the erythrocytic metabolism. Using this strategy, we have obtained unprecedented nanocarrier targeting to early intraerythrocytic stages of the malaria parasite for which there is a lack of specific extracellular molecular tags. Polyethylene glycol-coated liposomes conjugated with monoclonal antibodies specific for the erythrocyte surface protein glycophorin A (anti-GPA iLP) were capable of targeting 100% RBCs and pRBCs at the low concentration of 0.5 μM total lipid in the culture, with >95% of added iLPs retained into the cells. When exposed for only 15 min to P. falciparum in vitro cultures synchronized at early stages, free CQ had no significant effect over parasite viability up to 200 nM drug, whereas iLP-encapsulated 50 nM CQ completely arrested its growth. Furthermore, when assayed in vivo in P. falciparum-infected humanized mice, anti-GPA iLPs cleared the pathogen below detectable levels at a CQ dose of 0.5 mg/kg. In comparison, free CQ administered at 1.75 mg/kg was, at most, 40-fold less efficient. Our data suggest that this significant improvement in drug antimalarial efficacy is in part due to a prophylactic effect of CQ found by the pathogen in its host cell right at the very moment of invasion.

Keywords: immunoliposomal nanoparticles, malaria, prophylactic-therapeutic polyvalent activity, targeted drug delivery

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198 Spatial Design Transformation of Mount Merapi's Dwellings Using Diachronic Approach

Authors: Catharina Dwi Astuti Depari, Gregorius Agung Setyonugroho

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In concern for human safety, living in disaster-prone areas is twofold: it is profoundly cataclysmic yet perceptibly contributive. This paradox could be identified in Kalitengah Lor Sub-village community who inhabit Mount Merapi’s most hazardous area, putting them to the highest exposure to eruptions’ cataclysmic impacts. After the devastating incident in 2010, through the Action Plan for Rehabilitation and Reconstruction, the National Government with immediate aid from humanitarian agencies initiated a relocation program by establishing nearly 2,613 temporary shelters throughout the mountain’s region. The problem arose as some of the most affected communities including those in Kalitengah Lor Sub-village, persistently refused to relocate. The obnoxious experience of those living in temporary shelters resulted from the program’s failure to support a long-term living was assumed to instigate the rejection. From the psychological standpoint, this phenomenon reflects the emotional bond between the affected communities with their former dwellings. Regarding this, the paper aims to reveal the factors influencing the emotional attachment of Kalitengah Lor community to their former dwellings including the dwellings’ spatial design transformation prior and post the eruption in 2010. The research adopted Likert five scale-questionnaire comprising a wide range of responses from strongly agree to strongly disagree. The responses were then statistically measured, leading to consensus that provides bases for further interpretations toward the local’s characteristics. Using purposive unit sampling technique, 50 respondents from 217 local households were randomly selected. Questions in the questionnaire were developed with concerns on the aspects of place attachment concept: affection, cognitive, behavior, and perception. Combined with quantitative method, the research adopted diachronic method which was aimed to analyze the spatial design transformation of each dwelling in relation to the inhabitant’s daily activities and personal preferences. The research found that access to natural resources like sand mining, agricultural farms and wood forests, social relationship and physical proximity from house to personal asset like cattle shed, are the dominant factors encouraging the locals to emotionally attached to their former dwellings. Consequently, each dwelling’s spatial design is suffered from changes in which the current house is typically larger in dimension and the bathroom is replaced by public toilet located outside the house’s backyard. Relatively unchanged, the cattle shed is still located in front of the house, the continuous visual relationship, particularly between the living and family room, is maintained, as well as the main orientation of the house towards the local street.

Keywords: diachronic method, former dwellings, local’s characteristics, place attachment, spatial design transformation

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197 Mobile Phones, (Dis) Empowerment and Female Headed Households: Trincomalee, Sri Lanka

Authors: S. A. Abeykoon

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This study explores the empowerment potential of the mobile phone, the widely penetrated and greatly affordable communication technology in Sri Lanka, for female heads of households in Trincomalee District, Sri Lanka-an area recovering from the effects of a 30-year civil war and the 2004 Boxing Day Tsunami. It also investigates how the use of mobile phones by these women is shaped and appropriated by the gendered power relations and inequalities in their respective communities and by their socio-economic factors and demographic characteristics. This qualitative study is based on the epistemology of constructionism; interpretivist, functionalist and critical theory approaches; and the process of action research. The data collection was conducted from September 2014 to November 2014 in two Divisional Secretaries of the Trincomalee District, Sri Lanka. A total of 30 semi-structured depth interviews and six focus groups with the female heads of households of Sinhalese, Tamil and Muslim ethnicities were conducted using purposive, representative and snowball sampling methods. The Grounded theory method was used to analyze transcribed interviews, focus group discussions and field notes that were coded and categorized in accordance with the research questions and the theoretical framework of the study. The findings of the study indicated that the mobile phone has mainly enabled the participants to balance their income earning activities and family responsibilities and has been useful in maintaining their family and social relationships, occupational duties and in making decisions. Thus, it provided them a higher level of security, safety, reassurance and self-confidence in carrying out their daily activities. They also practiced innovative strategies for the effective and efficient use of their mobile expenses. Although participants whose husbands or relatives have migrated were more tended to use smart phones, mobile literacy level of the majority of the participants was at a lower level limited to making and receiving calls and using SMS (Short Message Service) services. However, their interaction with the mobile phone was significantly shaped by the gendered power relations and their multiple identities based on their ethnicity, religion, class, education, profession and age. Almost all the participants were precautious of giving their mobile numbers to and have been harassed with ‘nuisance calls’ from men. For many, ownership and use of their mobile phone was shaped and influenced by their children and migrated husbands. Although these practices limit their use of the technology, there were many instances that they challenged these gendered harassments. While man-made and natural destructions have disempowered and victimized the women in the Sri Lankan society, they have also liberated women making them stronger and transforming their agency and traditional gender roles. Therefore, their present position in society is reflected in their mobile phone use as they assist such women to be more self-reliant and liberated, yet making them disempowered at some time.

Keywords: mobile phone, gender power relations, empowerment, female heads of households

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196 Dynamic Changes in NT-proBNP Levels in Unrelated Donors during Hematopoietic Stem Cells Mobilization

Authors: Natalia V. Minaeva, Natalia A. Zorina, Marina N. Khorobrikh, Philipp S. Sherstnev, Tatiana V. Krivokorytova, Alexander S. Luchinin, Maksim S. Minaev, Igor V. Paramonov

Abstract:

Background. Over the last few decades, the Center for International Blood and Marrow Transplant Research (CIBMTR) and the World Marrow Donor Association (WMDA) have been actively working to ensure the safety of the hematopoietic stem cell (HSC) donation process. Registration of adverse events that may occur during the donation period and establishing a relationship between donation and side effects are included in the WMDA international standards. The level of blood serum N-terminal pro-brain natriuretic peptide (NT-proBNP) is an early marker of myocardial stress. Due to the high analytical sensitivity and specificity, laboratory assessment of NT-proBNP makes it possible to objectively diagnose myocardial dysfunction. It is well known that the main stimulus for proBNP synthesis and secretion from atrial and ventricular cardiac myocytes is myocyte stretch and increasement of myocardial extensibility and pressure in the heart chambers. Аim. The aim of the study was to assess the dynamic changes in the levels of blood serum N-terminal pro-brain natriuretic peptide of unrelated donors at various stages of hematopoietic stem cell mobilization. Materials. We have examined 133 unrelated donors, including 92 men and 41 women, that have been included into the study. The NT-proBNP levels were measured before the start of mobilization, then on the day of apheresis, and after the donation of allogeneic HSC. The relationship between NT-proBNP levels and body mass index (BMI), ferritin, hemoglobin, and white blood cells (WBC) levels was assessed on the day of apheresis. The median age of donors was 34 years. Mobilization of HSCs was managed with filgrastim administration at a dose of 10 μg/kg daily for 4-5 days. The first leukocytapheresis was performed on day 4 from the start of filgrastim administration. Quantitative values of the blood serum NT-proBNP level are presented as a median (Me), first and third quartiles (Q1-Q3). Comparative analysis was carried out using the t-test and correlation analysis as well by Spearman method. Results. The baseline blood serum NT-proBNP levels in all 133 donors were within the reference values (<125 pg/ml) and equaled 21,6 (10,0; 43,3) pg/ml. At the same time, the level of NT-proBNP in women was significantly higher than that of men. On the day of the HSC apheresis, a significant increase of blood serum NT-proBNP levels was detected and equald 131,2 (72,6; 165,3) pg/ml (p<0,001), with higher rates in female donors. A statistically significant weak inverse correleation was established between the level of NT-proBNP and the BMI of donors (-0.18, p = 0,03), as well as the level of hemoglobin (-0.33, p <0,001), and ferritin levels (-0.19, p = 0,03). No relationship has been established between the magnitude of WBC levels achieved as a result of the mobilization of HSC on the day of leukocytapheresis. A day after the apheresis, the blood serum NT-proBNP levels still exceeded the reference values, but there was a decreasing tendency. Conclusion. An increase of the blood serum NT-proBNP level in unrelated donors during the mobilization of HSC was established. Future studies should clarify the reason for this phenomenon, as well as its effects on donors' long-term health.

Keywords: unrelated donors, mobilization, hematopoietic stem cells, N-terminal pro-brain natriuretic peptide

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195 Defective Autophagy Disturbs Neural Migration and Network Activity in hiPSC-Derived Cockayne Syndrome B Disease Models

Authors: Julia Kapr, Andrea Rossi, Haribaskar Ramachandran, Marius Pollet, Ilka Egger, Selina Dangeleit, Katharina Koch, Jean Krutmann, Ellen Fritsche

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It is widely acknowledged that animal models do not always represent human disease. Especially human brain development is difficult to model in animals due to a variety of structural and functional species-specificities. This causes significant discrepancies between predicted and apparent drug efficacies in clinical trials and their subsequent failure. Emerging alternatives based on 3D in vitro approaches, such as human brain spheres or organoids, may in the future reduce and ultimately replace animal models. Here, we present a human induced pluripotent stem cell (hiPSC)-based 3D neural in a vitro disease model for the Cockayne Syndrome B (CSB). CSB is a rare hereditary disease and is accompanied by severe neurologic defects, such as microcephaly, ataxia and intellectual disability, with currently no treatment options. Therefore, the aim of this study is to investigate the molecular and cellular defects found in neural hiPSC-derived CSB models. Understanding the underlying pathology of CSB enables the development of treatment options. The two CSB models used in this study comprise a patient-derived hiPSC line and its isogenic control as well as a CSB-deficient cell line based on a healthy hiPSC line (IMR90-4) background thereby excluding genetic background-related effects. Neurally induced and differentiated brain sphere cultures were characterized via RNA Sequencing, western blot (WB), immunocytochemistry (ICC) and multielectrode arrays (MEAs). CSB-deficiency leads to an altered gene expression of markers for autophagy, focal adhesion and neural network formation. Cell migration was significantly reduced and electrical activity was significantly increased in the disease cell lines. These data hint that the cellular pathologies is possibly underlying CSB. By induction of autophagy, the migration phenotype could be partially rescued, suggesting a crucial role of disturbed autophagy in defective neural migration of the disease lines. Altered autophagy may also lead to inefficient mitophagy. Accordingly, disease cell lines were shown to have a lower mitochondrial base activity and a higher susceptibility to mitochondrial stress induced by rotenone. Since mitochondria play an important role in neurotransmitter cycling, we suggest that defective mitochondria may lead to altered electrical activity in the disease cell lines. Failure to clear the defective mitochondria by mitophagy and thus missing initiation cues for new mitochondrial production could potentiate this problem. With our data, we aim at establishing a disease adverse outcome pathway (AOP), thereby adding to the in-depth understanding of this multi-faced disorder and subsequently contributing to alternative drug development.

Keywords: autophagy, disease modeling, in vitro, pluripotent stem cells

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194 A Systematic Review of Forest School for Early Childhood Education in China: Lessons Learned from European Studies from a Perspective of Ecological System

Authors: Xiaoying Zhang

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Forest school – an outdoor educational experience that is undertaken in an outdoor environment with trees – becomes an emerging field of early childhood education recently. In China, the benefits of natural outdoor education to children and young people’s wellness have raised attention. Although different types of outdoor-based activities have been involved in some pre-school of China, few study and practice have been conducted in terms of the notion of forest school. To comprehend the impact of forest school for children and young people, this study aims to systematically review articles on the topic of forest school in preschool education from an ecological perspective, i.e. from individual level (e.g., behavior and mental health) to microsystem level (e.g., the relationship between teachers and children) to ecosystem level. Based on PRISMA framework flow, using the key words of “Forest School” and “Early Childhood Education” for searching in Web-of-science database, a total of 33 articles were identified. Sample participants of 13 studies were not preschool children, five studies were not on forest school theme, and two literature review articles were excluded for further analysis. Finally, 13 articles were eligible for thematic analysis. According to Bronfenbrenner's ecological systems theory, there are some fingdings, on the individual level, current forest school studies are concerned about the children behavioral experience in forest school, how these experience may relate to their achievement or to develop children’s wellbeing/wellness, and how this type of learning experience may enhance children’s self-awareness on risk and safety issues. On the microsystem/mesosystem level, this review indicated that pedagogical development for forest school, risk perception from teachers and parents, social development between peers, and adult’s role in the participation of forest school were concerned, explored and discussed most frequently. On the macrosystem, the conceptualization of forest school is the key theme. Different forms of presentation in various countries with diverse cultures could provide various models of forest school education. However, there was no study investigating forest school on an ecosystem level. As for the potential benefits of physical health and mental wellness that results from forest school, it informs us to reflect the system of preschool education from the ecological perspective for Chinese children. For instance, most Chinese kindergartens ignored the significance of natural outdoor activities for children. Preschool education in China is strongly oriented by primary school system, which means pre-school children are expected to be trained as primary school students to do different subjects, such as math. Hardly any kindergarteners provide the opportunities for children and young people to take risks in a natural environment like forest school does. However, merely copying forest school model for a Chinese preschool education system will be less effective. This review of different level concerns could inform us that the localization the idea of forest school to adapt to a Chinese political, educational and cultural background. More detailed results and profound discussions will be presented in the full paper.

Keywords: early childhood education, ecological system, education development prospects in China, forest school

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193 Evaluation of Magnificent Event of India with Special Reference to Maha Kumbha Mela (Fair) 2013-A Congregation of Millions

Authors: Sharad Kumar Kulshreshtha

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

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

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