Search results for: patient care and safety

Authors: Abdou Elhendy

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Numerous study have shown the efficacy of the percutaneous intervention (PCI) and coronary stenting in improving left ventricular function and relieving exertional angina. Furthermore, PCI remains the main line of therapy in acute myocardial infarction. Improvement of procedural techniques and new devices have resulted in an increased number of PCI in those with difficult and extensive lesions, multivessel disease as well as total occlusion. Immediate and late outcome may be compromised by acute thrombosis or the development of fibro-intimal hyperplasia. In addition, progression of coronary artery disease proximal or distal to the stent as well as in non-stented arteries is not uncommon. As a result, complications can occur, such as acute myocardial infarction, worsened heart failure or recurrence of angina. In a stent, restenosis can occur without symptoms or with atypical complaints rendering the clinical diagnosis difficult. Routine invasive angiography is not appropriate as a follow up tool due to associated risk and cost and the limited functional assessment. Exercise and pharmacologic stress testing are increasingly used to evaluate the myocardial function, perfusion and adequacy of revascularization. Information obtained by these techniques provide important clues regarding presence and severity of compromise in myocardial blood flow. Stress echocardiography can be performed in conjunction with exercise or dobutamine infusion. The diagnostic accuracy has been moderate, but the results provide excellent prognostic stratification. Adding myocardial contrast agents can improve imaging quality and allows assessment of both function and perfusion. Stress radionuclide myocardial perfusion imaging is an alternative to evaluate these patients. The extent and severity of wall motion and perfusion abnormalities observed during exercise or pharmacologic stress are predictors of survival and risk of cardiac events. According to current guidelines, stress echocardiography and radionuclide imaging are considered to have appropriate indication among patients after PCI who have cardiac symptoms and those who underwent incomplete revascularization. Stress testing is not recommended in asymptomatic patients, particularly early after revascularization, Coronary CT angiography is increasingly used and provides high sensitive for the diagnosis of coronary artery stenosis. Average sensitivity and specificity for the diagnosis of in stent stenosis in pooled data are 79% and 81%, respectively. Limitations include blooming artifacts and low feasibility in patients with small stents or thick struts. Anatomical and functional cardiac imaging modalities are corner stone for the assessment of patients after PCI and provide salient diagnostic and prognostic information. Current imaging techniques cans serve as gate keeper for coronary angiography, thus limiting the risk of invasive procedures to those who are likely to benefit from subsequent revascularization. The determination of which modality to apply requires careful identification of merits and limitation of each technique as well as the unique characteristic of each individual patient.

Keywords: coronary artery disease, stress testing, cardiac imaging, restenosis

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

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

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

Procedia PDF Downloads 115

Authors: Anthony Nyamekeh-Armah Adjei, Toshiaki Aoki

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The unreliable and poor efficiency of electricity distribution leading to frequent power outages and high losses are the major challenge facing the power distribution sector in Ghana. Distribution system routes electricity from the power generating station at a higher voltage through the transmission grid and steps it down through the low voltage lines to end users. Approximately all electricity problems and disturbances that have increased the call for renewable and sustainable energy in recent years have their roots in the distribution system. Therefore, sustaining electricity distribution efficiency can potentially contribute to the reserve of natural energy resources use in power generation, reducing greenhouse gas emission (GHG), decreasing tariffs for consumers and effective human security. Human Security is a people-centered approach where individual human being is the principal object of concern, focuses on protecting the vital core of all human lives in ways for meeting basic needs that enhance the safety and protection of individuals and communities. The vulnerability is the diminished capacity of an individual or group to anticipate, resist and recover from the effect of natural, human-induced disaster. The research objectives are to explore the causes of frequent power outages to consumers, high losses in the distribution network and the effect of poor electricity distribution efficiency on the vulnerable (poor and ordinary) people that mostly depend on electricity for their daily activities or life to survive. The importance of the study is that in a developing country like Ghana where raising a capital for new infrastructure project is difficult, it would be beneficial to enhance the efficiency that will significantly minimize the high energy losses, reduce power outage, to ensure safe and reliable delivery of electric power to consumers to secure the security of people’s livelihood. The methodology used in this study is both interview and questionnaire survey to analyze the response from the respondents on causes of power outages and high losses facing the electricity company of Ghana (ECG) and its effect on the livelihood on the vulnerable people. Among the outcome of both administered questionnaire and the interview survey from the field were; poor maintenance of existing sub-stations, use of aging equipment, use of poor distribution infrastructure and poor metering and billing system. The main observation of this paper is that the poor network efficiency (high losses and power outages) affects the livelihood of the vulnerable people. Therefore, the paper recommends that policymakers should insist on all regulation guiding electricity distribution to improve system efficiency. In conclusion, there should be decentralization of off-grid solar PV technologies to provide a sustainable and cost-effective, which can increase daily productivity and improve the quality of life of the vulnerable people in the rural communities.

Keywords: electricity efficiency, high losses, human security, power outage

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

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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

Procedia PDF Downloads 118

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

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

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

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Authors: Daniel Thompson, Muhammad Peerbux, Sophie Cerutti, Hansraj Bookun

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Introduction: Dialysis access is a key component of the care of patients with end stage renal failure. In our institution, a combined service of vascular surgeons and nephrologists are responsible for the creation and maintenance of arteriovenous fisultas (AVF), tenckhoff cathethers and Hickman/permcath lines. This poster investigates the last 10 years of dialysis access surgery conducted at St. Vincent’s Hospital Melbourne. Method: A cross-sectional retrospective analysis was conducted of patients of St. Vincent’s Hospital Melbourne (Victoria, Australia) utilising data collection from the Australasian Vascular Audit (Australian and New Zealand Society for Vascular Surgery). Descriptive demographic analysis was carried out as well as operation type, length of hospital stays, postoperative deaths and need for reoperation. Results: 2085 patients with renal failure were operated on between the years of 2011 and 2020. 1315 were male (63.1%) and 770 were female (36.9%). The mean age was 58 (SD 13.8). 92% of patients scored three or greater on the American Society of Anesthiologiests classification system. Almost half had a history of ischaemic heart disease (48.4%), more than half had a history of diabetes (64%), and a majority had hypertension (88.4%). 1784 patients had a creatinine over 150mmol/L (85.6%), the rest were on dialysis (14.4%). The most common access procedure was AVF creation, with 474 autologous AVFs and 64 prosthetic AVFs. There were 263 Tenckhoff insertions. We performed 160 cadeveric renal transplants. The most common location for AVF formation was brachiocephalic (43.88%) followed by radiocephalic (36.7%) and brachiobasilic (16.67%). Fistulas that required re-intervention were most commonly angioplastied (n=163), followed by thrombectomy (n=136). There were 107 local fistula repairs. Average length of stay was 7.6 days, (SD 12). There were 106 unplanned returns to theatre, most commonly for fistula creation, insertion of tenckhoff or permacath removal (71.7%). There were 8 deaths in the immediately postoperative period. Discussion: Access to dialysis is vital for patients with end stage kidney disease, and requires a multidisciplinary approach from both nephrologists, vascular surgeons, and allied health practitioners. Our service provides a variety of dialysis access methods, predominately fistula creation and tenckhoff insertion. Patients with renal failure are heavily comorbid, and prolonged hospital admission following surgery is a source of significant healthcare expenditure. AVFs require careful monitoring and maintenance for ongoing utility, and our data reflects a multitude of operations required to maintain usable access. The requirement for dialysis is growing worldwide and our data demonstrates a local experience in access, with preferred methods, common complications and the associated surgical interventions.

Keywords: dialysis, fistula, nephrology, vascular surgery

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Authors: Luisa Windhagen, Atsumi Hirose, Alex Bottle

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Global urbanization has resulted in the expansion of slums, leaving over 10 million Tanzanians in urban poverty and at risk of poor health. Whilst rural residence has historically been associated with an increased risk of adverse pregnancy outcomes, recent studies found higher perinatal mortality rates in urban Tanzania. This study aims to understand to what extent slum neighborhoods may account for the spatial disparities seen in Tanzania. We generated a slum indicator based on UN-HABITAT criteria to identify slum clusters within the 2015-2016 Tanzania Demographic and Health Survey. Descriptive statistics, disaggregated by urban slum, urban non-slum, and rural areas, were produced. Simple and multivariable logistic regression examined the association between cluster residence type and neonatal mortality and stillbirth. For neonatal mortality, we additionally built a multilevel logistic regression model, adjusting for confounding and clustering. The neonatal mortality ratio was highest in slums (38.3 deaths per 1000 live births); the stillbirth rate was three times higher in slums (32.4 deaths per 1000 births) than in urban non-slums. Neonatal death was more likely to occur in slums than in urban non-slums (aOR=2.15, 95% CI=1.02-4.56) and rural areas (aOR=1.78, 95% CI=1.15-2.77). Odds of stillbirth were over five times higher among rural than urban non-slum residents (aOR=5.25, 95% CI=1.31-20.96). The results suggest that slums contribute to the urban disadvantage in Tanzanian neonatal health. Higher neonatal mortality in slums may be attributable to lack of education, lower socioeconomic status, poor healthcare access, and environmental factors, including indoor and outdoor air pollution and unsanitary conditions from inadequate housing. However, further research is required to ascertain specific causalities as well as significant associations between residence type and other pregnancy outcomes. The high neonatal mortality, stillbirth, and slum formation rates in Tanzania signify that considerable change is necessary to achieve international goals for health and human settlements. Disparities in access to adequate housing, safe water and sanitation, high standard antenatal, intrapartum, and neonatal care, and maternal education need to urgently be addressed. This study highlights the spatial neonatal mortality shift from rural settings to urban informal settlements in Tanzania. Importantly, other low- and middle-income countries experiencing overwhelming urbanization and slum expansion may also be at risk of a reversing trend in residential neonatal health differences.

Keywords: urban health, slum residence, neonatal mortality, stillbirth, global urbanisation

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Authors: Ayesha Mushtaq

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Asthma is a pulmonary disease in which blockade of the airway takes place due to inflammation as a response to certain allergens. Breathing troubles, cough, and dyspnea are one of the few symptoms. Several studies have indicated a significant effect on asthma due to changes in dietary routines. Certain food items, such as oily foods and other materials, are known to cause an increase in the symptoms of asthma. Low dietary intake of fruits and vegetables may be important in relation to asthma prevalence. The objective of this study is to assess and compare the nutritional status of asthmatic and non-asthmatic patients. The significance of this study lies in the factor that it will help nutritionists to arrange a feasible dietary routine for asthmatic patients. This research was conducted at the Pulmonology Department of the Pakistan Institute of Medical Science Islamabad. About thirty hundred thirty-four million people are affected by asthma worldwide. Pakistan is on the verge of being an uplifted urban population and asthma cases are increasingly high these days. Several studies suggest an increase in the Asthmatic patient population due to improper diet. 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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Authors: Evangelos Kaisar, Anika Tabassum, Taraneh Ardalan, Majed Al-Ghandour

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The economy of any country is dependent on its ability to accommodate the movement and delivery of goods. The demand for goods movement and services increases truck traffic on highways and inside the cities. The livability of most cities is directly affected by the congestion and environmental impacts of trucks, which are the backbone of the urban freight system. Better operation of heavy vehicles on highways and arterials could lead to the network’s efficiency and reliability. In many cases, roundabouts can respond better than at-level intersections to enable traffic operations with increased safety for both cars and heavy vehicles. Recently emerged, the concept of turbo-roundabout is a viable alternative to the two-lane roundabout aiming to improve traffic efficiency. The primary objective of this study is to evaluate the operation and performance level of an at-grade intersection, a conventional two-lane roundabout, and a basic turbo roundabout for freight movements. To analyze and evaluate the performances of the signalized intersections and the roundabouts, micro simulation models were developed PTV VISSIM. The networks chosen for this analysis in this study are to experiment and evaluate changes in the performance of the movement of vehicles with different geometric and flow scenarios. There are several scenarios that were examined when attempting to assess the impacts of various geometric designs on vehicle movements. The overall traffic efficiency depends on the geometric layout of the intersections, which consists of traffic congestion rate, hourly volume, frequency of heavy vehicles, type of road, and the ratio of major-street versus side-street traffic. The traffic performance was determined by evaluating the delay time, number of stops, and queue length of each intersection for varying truck percentages. The results indicate that turbo-roundabouts can replace signalized intersections and two-lane roundabouts only when the traffic demand is low, even with high truck volume. More specifically, it is clear that two-lane roundabouts are seen to have shorter queue lengths compared to signalized intersections and turbo-roundabouts. For instance, considering the scenario where the volume is highest, and the truck movement and left turn movement are maximum, the signalized intersection has 3 times, and the turbo-roundabout has 5 times longer queue length than a two-lane roundabout in major roads. Similarly, on minor roads, signalized intersections and turbo-roundabouts have 11 times longer queue lengths than two-lane roundabouts for the same scenario. As explained from all the developed scenarios, while the traffic demand lowers, the queue lengths of turbo-roundabouts shorten. This proves that turbo roundabouts perform well for low and medium traffic demand. The results indicate that turbo-roundabouts can replace signalized intersections and two-lane roundabouts only when the traffic demand is low, even with high truck volume. Finally, this study provides recommendations on the conditions under which different intersections perform better than each other.

Keywords: At-grade intersection, simulation, turbo-roundabout, two-lane roundabout

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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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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

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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

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

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

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

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Authors: Ekin Esen, Mohammad Alipour, Riza Kizilel

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Rechargeable lithium-ion batteries have been replacing lead-acid batteries for the last decade due to their outstanding properties such as high energy density, long shelf life, and almost no memory effect. Besides these, being very light compared to lead acid batteries has gained them their dominant place in the portable electronics market, and they are now the leading candidate for electric vehicles (EVs) and hybrid electric vehicles (HEVs). However, their performance strongly depends on temperature, and this causes some inconveniences for their utilization in extreme temperatures. Since weather conditions vary across the globe, this situation limits their utilization for EVs and HEVs and makes a thermal management system obligatory for the battery units. The objective of this study is to understand thermal characteristics of Li-ion battery modules for various operation conditions and design a thermal management system to enhance battery performance in EVs and HEVs. In the first part of our study, we investigated thermal behavior of commercially available pouch type 20Ah LiFePO₄ (LFP) cells under various conditions. Main parameters were chosen as ambient temperature and discharge current rate. Each cell was charged and discharged at temperatures of 0°C, 10°C, 20°C, 30°C, 40°C, and 50°C. The current rate of charging process was 1C while it was 1C, 2C, 3C, 4C, and 5C for discharge process. Temperatures of 7 different points on the cells were measured throughout charging and discharging with N-type thermocouples, and a detailed temperature profile was obtained. In the second part of our study, we connected 4 cells in series by clinching and prepared 4S1P battery modules similar to ones in EVs and HEVs. Three reference points were determined according to the findings of the first part of the study, and a thermocouple is placed on each reference point on the cells composing the 4S1P battery modules. In the end, temperatures of 6 points in the module and 3 points on the top surface were measured and changes in the surface temperatures were recorded for different discharge rates (0.2C, 0.5C, 0.7C, and 1C) at various ambient temperatures (0°C – 50°C). Afterwards, aluminum plates with channels were placed between the cells in the 4S1P battery modules, and temperatures were controlled with airflow. Airflow was provided with a regular compressor, and the effect of flow rate on cell temperature was analyzed. Diameters of the channels were in mm range, and shapes of the channels were determined in order to make the cell temperatures uniform. Results showed that the designed thermal management system could help keeping the cell temperatures in the modules uniform throughout charge and discharge processes. Other than temperature uniformity, the system was also beneficial to keep cell temperature close to the optimum working temperature of Li-ion batteries. It is known that keeping the temperature at an optimum degree and maintaining uniform temperature throughout utilization can help obtaining maximum power from the cells in battery modules for a longer time. Furthermore, it will increase safety by decreasing the risk of thermal runaways. Therefore, the current study is believed to be beneficial for wider use of Li batteries for battery modules of EVs and HEVs globally.

Keywords: lithium ion batteries, thermal management system, electric vehicles, hybrid electric vehicles

Procedia PDF Downloads 140

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

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Authors: Niyongabo Elyse

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Prefabricated building construction is a pioneering approach that combines design, production, and assembly to attain energy efficiency, environmental sustainability, and economic feasibility. Despite continuous development in the industry in China, the low technical maturity of standardized design, factory production, and construction assembly introduces uncertainties affecting prefabricated component production and on-site assembly processes. This research focuses on enhancing project management performance under uncertainty to help enterprises navigate these challenges and optimize project resources. The study introduces a perspective on how uncertain factors influence the implementation of prefabricated building construction projects. It proposes a theoretical model considering project process management ability, adaptability to uncertain environments, and collaboration ability of project participants. The impact of uncertain factors is demonstrated through case studies and quantitative analysis, revealing constraints on implementation time, cost, quality, and safety. To address uncertainties in prefabricated component production scheduling, a fuzzy model is presented, expressing processing times in interval values. The model utilizes a cooperative co-evolution evolution algorithm (CCEA) to optimize scheduling, demonstrated through a real case study showcasing reduced project duration and minimized effects of processing time disturbances. Additionally, the research addresses on-site assembly construction scheduling, considering the relationship between task processing times and assigned resources. A multi-objective model with fuzzy activity durations is proposed, employing a hybrid cooperative co-evolution evolution algorithm (HCCEA) to optimize project scheduling. Results from real case studies indicate improved project performance in terms of duration, cost, and resilience to processing time delays and resource changes. The study also introduces a multistage dynamic process control model, utilizing IoT technology for real-time monitoring during component production and construction assembly. This approach dynamically adjusts schedules when constraints arise, leading to enhanced project management performance, as demonstrated in a real prefabricated housing project. Key contributions include a fuzzy prefabricated components production scheduling model, a multi-objective multi-mode resource-constrained construction project scheduling model with fuzzy activity durations, a multi-stage dynamic process control model, and a cooperative co-evolution evolution algorithm. The integrated mathematical model addresses the complexity of prefabricated building construction project management, providing a theoretical foundation for practical decision-making in the field.

Keywords: prefabricated construction, project management performance, uncertainty, fuzzy scheduling

Procedia PDF Downloads 31

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 300

Authors: Akmez Nabeerasool, Michaelis Massaros, Nigel Brown, David Sanderson, David Parocki, Charlotte Thompson, Mike Lodge, Mikael Khan

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The provision of clean and safe drinking water is of paramount importance and is a basic human need. Water scarcity coupled with tightening of regulations and the inability of current treatment technologies to deal with emerging contaminants and Pharmaceuticals and personal care products means that alternative treatment technologies that are viable and cost effective are required in order to meet demand and regulations for clean water supplies. Logistically, the application of water treatment in rural areas presents unique challenges due to the decentralisation of abstraction points arising from low population density and the resultant lack of infrastructure as well as the need to treat water at the site of use. This makes it costly to centralise treatment facilities and hence provide potable water direct to the consumer. Furthermore, across the UK there are segments of the population that rely on a private water supply which means that the owner or user(s) of these supplies, which can serve one household to hundreds, are responsible for the maintenance. The treatment of these private water supply falls on the private owners, and it is imperative that a chemical free technological solution that can operate unattended and does not produce any waste is employed. Arvia’s patented advanced oxidation technology combines the advantages of adsorption and electrochemical regeneration within a single unit; the Organics Destruction Cell (ODC). The ODC uniquely uses a combination of adsorption and electrochemical regeneration to destroy organics. Key to this innovative process is an alternative approach to adsorption. The conventional approach is to use high capacity adsorbents (e.g. activated carbons with high porosities and surface areas) that are excellent adsorbents, but require complex and costly regeneration. Arvia’s technology uses a patent protected adsorbent, Nyex™, which is a non-porous, highly conductive, graphite based adsorbent material that enables it to act as both the adsorbent and as a 3D electrode. Adsorbed organics are oxidised and the surface of the Nyex™ is regenerated in-situ for further adsorption without interruption or replacement. Treated water flows from the bottom of the cell where it can either be re-used or safely discharged. Arvia™ Technology Ltd. has trialled the application of its tertiary water treatment technology in treating reservoir water abstracted near Glasgow, Scotland, with promising results. Several other pilot plants have also been successfully deployed at various locations in the UK showing the suitability and effectiveness of the technology in removing recalcitrant organics (including pharmaceuticals, steroids and hormones), COD and colour.

Keywords: Arvia™ process, adsorption, water treatment, electrochemical oxidation

Procedia PDF Downloads 241

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

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Authors: Shayma Mohammed, Adel Trabelsi

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Radiopharmacy is the art of preparing high-quality, radioactive, medicinal products for use in diagnosis and therapy. Radiopharmaceuticals unlike normal medicines, this dual aspect (radioactive, medical) makes their management highly critical. One of the most convincing applications of modern technologies is the ability to delegate the execution of repetitive tasks to programming scripts. Automation has found its way to the most skilled jobs, to improve the company's overall performance by allowing human workers to focus on more important tasks than document filling. This project aims to contribute to implement a comprehensive system to insure rigorous management of radiopharmaceuticals through the use of a platform that links the Nuclear Medicine Service Management System to the Nuclear Radio-pharmacy Management System in accordance with the recommendations of World Health Organization (WHO) and International Atomic Energy Agency (IAEA). In this project we attempt to build a web application that targets radiopharmacies, the platform is built atop the inherently compatible web stack which allows it to work in virtually any environment. Different technologies are used in this project (PHP, Symfony, MySQL Workbench, Bootstrap, Angular 7, Visual Studio Code and TypeScript). The operating principle of the platform is mainly based on two parts: Radiopharmaceutical Backoffice for the Radiopharmacian, who is responsible for the realization of radiopharmaceutical preparations and their delivery and Medical Backoffice for the Doctor, who holds the authorization for the possession and use of radionuclides and he/she is responsible for ordering radioactive products. The application consists of sven modules: Production, Quality Control/Quality Assurance, Release, General Management, References, Transport and Stock Management. It allows 8 classes of users: The Production Manager (PM), Quality Control Manager (QCM), Stock Manager (SM), General Manager (GM), Client (Doctor), Parking and Transport Manager (PTM), Qualified Person (QP) and Technical and Production Staff. Digital platform bringing together all players involved in the use of radiopharmaceuticals and integrating the stages of preparation, production and distribution, Web technologies, in particular, promise to offer all the benefits of automation while requiring no more than a web browser to act as a user client, which is a strength because the web stack is by nature multi-platform. This platform will provide a traceability system for radiopharmaceuticals products to ensure the safety and radioprotection of actors and of patients. The new integrated platform is an alternative to write all the boilerplate paperwork manually, which is a tedious and error-prone task. It would minimize manual human manipulation, which has proven to be the main source of error in nuclear medicine. A codified electronic transfer of information from radiopharmaceutical preparation to delivery will further reduce the risk of maladministration.

Keywords: automated system, management, radiopharmacy, technical papers

Procedia PDF Downloads 136

Authors: Giovana Vesentini, Fernanda Piculo, Gabriela Marini, Debora Damasceno, Angelica Barbosa, Selma Martheus, Marilza Rudge

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Problem statement: Skeletal muscle is highly adaptable, muscle fiber composition and size can respond to a variety of stimuli, such physiologic, as pregnancy, and metabolic abnormalities, as Diabetes mellitus. This study aimed to analyze the effects of pregnancy-associated diabetes on the rectus abdominis muscle (RA), and to compare this changes in rats and women. Methods: Female Wistar rats were maintained under controlled conditions and distributed in Pregnant (P) and Long-term mild pregnant diabetic (LTMd) (n=3 r/group). Diabetes in rats was induced by streptozotocin (100mg/Kg, sc) on the first day of life, for a hyperglycemic state between 120-300 mg/dL in adult life. Female rats were mated overnight, at day 21 of pregnancy were anesthetized, and killed for the harvesting of maternal RA. Pregnant women who attended the Diabetes Prenatal Care Clinic of Botucatu Medical School were distributed in Pregnant non-diabetic (Pnd) and Gestational Diabetic (GDM) (n=3 w/group). The diagnosis of GDM was established according to ADA’s criteria (2016). The harvesting of RA was during the cesarean section. Transversal cross-sections of the RA of both women and rats were analyzed by transmission electron microscopy. All procedures were approved by the Ethics Committee on Animal Experiments of the Botucatu Medical School (Protocol Number 1003/2013) and by the Botucatu Medical School Ethical Committee for Human Research in Medical Sciences (CAAE: 41570815.0.0000.5411). Results: The photomicrographs of the RA of rats revealed disorganized Z lines, thinning sarcomeres, and a usual quantity of intermyofibrillar mitochondria in the P group. The LTMd group showed swollen sarcoplasmic reticulum, dilated T tubes and areas with sarcomere disruption. The ultrastructural analysis of Pnd non-diabetic women in the RA showed well-organized myofibrils forming intact sarcomeres, organized Z lines and a normal distribution of intermyofibrillar mitochondria. The GDM group revealed increase in intermyofibrillar mitochondria, areas with sarcomere disruption and increased lipid droplets. Conclusion: Pregnancy and diabetes induce adaptations in the ultrastructure of the rectus abdominis muscle for both women and rats, changing the architectural design of these tissues. However, in rats these changes are more severe maybe because, besides the high blood glucose levels, the quadrupedal animal may suffer an excessive mechanical tension during pregnancy by gravity. Probably, these findings may suggest that these alterations are a risk factor that contributes to the development of muscle dysfunction in women with GDM and may motivate treatment strategies in these patients.

Keywords: gestational diabetes, muscle dysfunction, pregnancy, rectus abdominis

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Authors: Priyanka Verma, Vijaya Dixit, Rishabh Bajpai

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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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Authors: Monica Sanchez

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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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Authors: Henry Venter, Murali Thyloth, Alceu Casseb

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Historically, mental and substance use disorders were not a global health priority. Since the 1993 World Development Report, the importance of the contribution of mental health and substance abuse on the relative global burden associated with disease morbidity has been recognized with 300 million people worldwide suffering from depression alone. This led to an international effort to improve the mental health of populations around the world. Despite these efforts some countries remain at the top of the list of countries with the highest rate of mental illness. Important research questions were asked: Would there be commonalities regarding mental health between these countries; would there be common factors leading to the high prevalence of mental illness; and how prepared are these countries with mental health delivery? Findings from this research can aid organizations and institutions preparing mental health service providers to focus training and preparation to address specific needs revealed by the study. Methods: Researchers decided to compare three distinctly different countries at the top of the list of countries with the highest rate of mental illness, the USA, India and Brazil, situated on three different continents with different economies and lifestyles. Data were collected using archival research methodology, reviewing records and findings of international and national health and mental health studies to subtract and compare data and findings. Results: The findings indicated that India is the most depressed country in the world, followed by the USA (and China) with Brazil in Latin America with the greatest number of depressed individuals. By 2020 roughly 20% of India, acountry of over one billion citizens, will suffer from some form of mental illnees, yet there are less than 4,000 experts available. In the USA 164.8 million people were substance abusers and an estimate of 47.6 million adults, 18 or older, had any mental illness in 2018. That means that about one in five adults in the USA experiences some form of mental illness each year, but only 41% of those affected received mental health care or services in the past year. Brazil has the greatest number of depressed individuals, in Latin America. Adults living in Sao Paulo megacity has prevalence of mental disorders at greater levels than similar surveys conducted in other areas of the world with more than one million adults with serious impairment levels. Discussion: The results show that, despite the vast socioeconomic differences between the three countries, there are correlations regarding mental health prevalence and difficulty to provide adequate services including a lack of awareness of how serious mental illness is, stigma for seeking mental illness, with comorbidity a common phenomenon, and a lack of partnership between different levels of service providers, which weakens mental health service delivery. The findings also indicate that mental health training institutions have a monumental task to prepare personnel to address the future mental health needs in each of the countries compared, which will constitute the next phase of the research.

Keywords: mental health epidemiology, mental health disorder, mental health prevalence, mental health treatment

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Authors: Ian Kingsbury

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The rapid expansion of charter schools (public schools that receive government but do not face the same regulations as traditional public schools) over the preceding two decades has raised concerns over the potential for graft and fraud. These concerns are largely justified: Incidents of financial crime and mismanagement are not unheard of, and the charter sector has become a darling of hedge fund managers. In response, several states have strengthened their charter school regulatory regimes. Imposing regulations and attempting to increase accountability seem like sensible measures, and perhaps they are necessary. However, increased regulation may come at the cost of imposing barriers to entry. Specifically, increased regulation often entails evidence for a high likelihood of fiscal solvency. That should theoretically entail access to capital in the short-term, which may systematically preclude Black or Hispanic applicants from opening charter schools. Moreover, increased regulation necessarily entails more red tape. The institutional wherewithal and the number of hours required to complete an application to open a charter school might favor those who have partnered with an education service provider, specifically a charter management organization (CMO) or education management organization (EMO). These potential barriers to entry pose a significant policy concern. Just as policymakers hope to increase the share of minority teachers and principals, they should sensibly care whether individuals who open charter schools look like the students in that school. Moreover, they might be concerned if successful applications in states with stringent regulations are overwhelmingly affiliated with education service providers. One of the original missions of charter schools was to serve as a laboratory of innovation. Approving only those applications affiliated with education service providers (and in effect establishing a parallel network of schools rather than a diverse marketplace of schools) undermines that mission. Data and methods: The analysis examines more than 2,000 charter school applications from 15 states. It compares the outcomes of applications from states with a strong regulatory environment (those with high scores) from NACSA-the National Association of Charter School Authorizers- to applications from states with a weak regulatory environment (those with a low NACSA score). If the hypothesis is correct, applicants not affiliated with an ESP are more likely to be rejected in high-regulation states compared to those affiliated with an ESP, and minority candidates not affiliated with an education service provider (ESP) are particularly likely to be rejected. Initial returns indicate that the hypothesis holds. More applications in low NASCA-scoring Arizona come from individuals not associated with an ESP, and those individuals are as likely to be accepted as those affiliated with an ESP. On the other hand, applicants in high-NACSA scoring Indiana and Ohio are more than 20 percentage points more likely to be accepted if they are affiliated with an ESP, and the effect is particularly pronounced for minority candidates. These findings should spur policymakers to consider the drawbacks of charter school accountability and consider accountability regimes that do not impose barriers to entry.

Keywords: accountability, barriers to entry, charter schools, choice

Procedia PDF Downloads 127

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

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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

Procedia PDF Downloads 348

Authors: Mary Deyo, Zmara Harrison

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This study reports the outcomes of an 8-week experiential learning program for 6 adults with Intellectual and Developmental Disabilities (IDD) at a day habilitation program. The intervention foci for this program include executive function, language learning in the domains of expressive, receptive, and pragmatic language, and quality of life. The interprofessional collaboration aimed at supporting adults with IDD to reach person-centered, functional goals across skill domains is critical. This study is a significant addition to the speech-language pathology literature in that it examines a therapy method that potentially meets this need while targeting domains within the speech-language pathology scope of practice. Communication therapy was provided during highly valued and meaningful hands-on learning experiences, referred to as the Garden Club, which incorporated all aspects of planting and caring for a garden as well as related journaling, sensory, cooking, art, and technology-based activities. Direct care staff and an undergraduate research assistant were trained by SLP to be impactful language guides during their interactions with participants in the Garden Club. SLP also provided direct therapy and modeling during Garden Club. Research methods used in this study included a mixed methods analysis of a literature review, a quasi-experimental implementation of communication therapy in the context of experiential learning activities, Quality of Life participant surveys, quantitative pre- post- data collection and linear mixed model analysis, qualitative data collection with qualitative content analysis and coding for themes. Outcomes indicated overall positive changes in expressive vocabulary, following multi-step directions, sequencing, problem-solving, planning, skills for building and maintaining meaningful social relationships, and participant perception of the Garden Project’s impact on their own quality of life. Implementation of this project also highlighted supports and barriers that must be taken into consideration when planning similar projects. Overall findings support the use of experiential learning projects in day habilitation programs for adults with IDD, as well as additional research to deepen understanding of best practices, supports, and barriers for implementation of experiential learning with this population. This research provides an important contribution to research in the fields of speech-language pathology and other professions serving adults with IDD by describing an interprofessional experiential learning program with positive outcomes for executive function, language learning, and quality of life.

Keywords: experiential learning, adults, intellectual and developmental disabilities, expressive language, receptive language, pragmatic language, executive function, communication therapy, day habilitation, interprofessionalism, quality of life

Procedia PDF Downloads 91

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

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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

Procedia PDF Downloads 339

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

Procedia PDF Downloads 102