Search results for: antimicrobial sensitivity
Commenced in January 2007
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Edition: International
Paper Count: 2665

Search results for: antimicrobial sensitivity

235 Monitoring Key Biomarkers Related to the Risk of Low Breastmilk Production in Women, Leading to a Positive Impact in Infant’s Health

Authors: R. Sanchez-Salcedo, N. H. Voelcker

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Currently, low breast milk production in women is one of the leading health complications in infants. Recently, It has been demonstrated that exclusive breastfeeding, especially up to a minimum of 6 months, significantly reduces respiratory and gastrointestinal infections, which are the main causes of death in infants. However, the current data shows that a high percentage of women stop breastfeeding their children because they perceive an inadequate supply of milk, and only 45% of children are breastfeeding under 6 months. It is, therefore, clear the necessity to design and develop a biosensor that is sensitive and selective enough to identify and validate a panel of milk biomarkers that allow the early diagnosis of this condition. In this context, electrochemical biosensors could be a powerful tool for assessing all the requirements in terms of reliability, selectivity, sensitivity, cost efficiency and potential for multiplex detection. Moreover, they are suitable for the development of POC devices and wearable sensors. In this work, we report the development of two types of sensing platforms towards several biomarkers, including miRNAs and hormones present in breast milk and dysregulated in this pathological condition. The first type of sensing platform consists of an enzymatic sensor for the detection of lactose, one of the main components in milk. In this design, we used gold surface as an electrochemical transducer due to the several advantages, such as the variety of strategies available for its rapid and efficient functionalization with bioreceptors or capture molecules. For the second type of sensing platform, nanoporous silicon film (pSi) was chosen as the electrode material for the design of DNA sensors and aptasensors targeting miRNAs and hormones, respectively. pSi matrix offers a large superficial area with an abundance of active sites for the immobilization of bioreceptors and tunable characteristics, which increase the selectivity and specificity, making it an ideal alternative material. The analytical performance of the designed biosensors was not only characterized in buffer but also validated in minimally treated breastmilk samples. We have demonstrated the potential of an electrochemical transducer on pSi and gold surface for monitoring clinically relevant biomarkers associated with the heightened risk of low milk production in women. This approach, in which the nanofabrication techniques and the functionalization methods were optimized to increase the efficacy of the biosensor highly provided a foundation for further research and development of targeted diagnosis strategies.

Keywords: biosensors, electrochemistry, early diagnosis, clinical markers, miRNAs

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234 Printed Electronics for Enhanced Monitoring of Organ-on-Chip Culture Media Parameters

Authors: Alejandra Ben-Aissa, Martina Moreno, Luciano Sappia, Paul Lacharmoise, Ana Moya

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Organ-on-Chip (OoC) stands out as a highly promising approach for drug testing, presenting a cost-effective and ethically superior alternative to conventional in vivo experiments. These cutting-edge devices emerge from the integration of tissue engineering and microfluidic technology, faithfully replicating the physiological conditions of targeted organs. Consequently, they offer a more precise understanding of drug responses without the ethical concerns associated with animal testing. When addressing the limitations of OoC due to conventional and time-consuming techniques, Lab-On-Chip (LoC) emerge as a disruptive technology capable of providing real-time monitoring without compromising sample integrity. This work develops LoC platforms that can be integrated within OoC platforms to monitor essential culture media parameters, including glucose, oxygen, and pH, facilitating the straightforward exchange of sensing units within a dynamic and controlled environment without disrupting cultures. This approach preserves the experimental setup, minimizes the impact on cells, and enables efficient, prolonged measurement. The LoC system is fabricated following the patented methodology protected by EU patent EP4317957A1. One of the key challenges of integrating sensors in a biocompatible, feasible, robust, and scalable manner is addressed through fully printed sensors, ensuring a customized, cost-effective, and scalable solution. With this technique, sensor reliability is enhanced, providing high sensitivity and selectivity for accurate parameter monitoring. In the present study, LoC is validated measuring a complete culture media. The oxygen sensor provided a measurement range from 0 mgO2/L to 6.3 mgO2/L. The pH sensor demonstrated a measurement range spanning 2 pH units to 9.5 pH units. Additionally, the glucose sensor achieved a measurement range from 0 mM to 11 mM. All the measures were performed with the sensors integrated in the LoC. In conclusion, this study showcases the impactful synergy of OoC technology with LoC systems using fully printed sensors, marking a significant step forward in ethical and effective biomedical research, particularly in drug development. This innovation not only meets current demands but also lays the groundwork for future advancements in precision and customization within scientific exploration.

Keywords: organ on chip, lab on chip, real time monitoring, biosensors

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233 Evaluating Viability of Using South African Forestry Process Biomass Waste Mixtures as an Alternative Pyrolysis Feedstock in the Production of Bio Oil

Authors: Thembelihle Portia Lubisi, Malusi Ntandoyenkosi Mkhize, Jonas Kalebe Johakimu

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Fertilizers play an important role in maintaining the productivity and quality of plants. Inorganic fertilizers (containing nitrogen, phosphorus, and potassium) are largely used in South Africa as they are considered inexpensive and highly productive. When applied, a portion of the excess fertilizer will be retained in the soil, a portion enters water streams due to surface runoff or the irrigation system adopted. Excess nutrient from the fertilizers entering the water stream eventually results harmful algal blooms (HABs) in freshwater systems, which not only disrupt wildlife but can also produce toxins harmful to humans. Use of agro-chemicals such as pesticides and herbicides has been associated with increased antimicrobial resistance (AMR) in humans as the plants are consumed by humans. This resistance of bacterial poses a threat as it prevents the Health sector from being able to treat infectious disease. Archaeological studies have found that pyrolysis liquids were already used in the time of the Neanderthal as a biocide and plant protection product. Pyrolysis is thermal degradation process of plant biomass or organic material under anaerobic conditions leading to production of char, bio-oils and syn gases. Bio-oil constituents can be categorized as water soluble (wood vinegar) and water insoluble fractions (tar and light oils). Wood vinegar (pyro-ligneous acid) is said to contain contains highly oxygenated compounds including acids, alcohols, aldehydes, ketones, phenols, esters, furans, and other multifunctional compounds with various molecular weights and compositions depending on the biomass material derived from and pyrolysis operating conditions. Various researchers have found the wood vinegar to be efficient in the eradication of termites, effective in plant protection and plant growth, has antibacterial characteristics and was found effective in inhibiting the micro-organisms such as candida yeast, E-coli, etc. This study investigated characterisation of South African forestry product processing waste with intention of evaluating the potential of using the respective biomass waste as feedstock for boil oil production via pyrolysis process. Ability to use biomass waste materials in production of wood-vinegar has advantages that it does not only allows for reduction of environmental pollution and landfill requirement, but it also does not negatively affect food security. The biomass wastes investigated were from the popular tree types in KZN, which are, pine saw dust (PSD), pine bark (PB), eucalyptus saw dust (ESD) and eucalyptus bark (EB). Furthermore, the research investigates the possibility of mixing the different wastes with an aim to lessen the cost of raw material separation prior to feeding into pyrolysis process and mixing also increases the amount of biomass material available for beneficiation. A 50/50 mixture of PSD and ESD (EPSD) and mixture containing pine saw dust; eucalyptus saw dust, pine bark and eucalyptus bark (EPSDB). Characterisation of the biomass waste will look at analysis such as proximate (volatiles, ash, fixed carbon), ultimate (carbon, hydrogen, nitrogen, oxygen, sulphur), high heating value, structural (cellulose, hemicellulose and lignin) and thermogravimetric analysis.

Keywords: characterisation, biomass waste, saw dust, wood waste

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232 Winter – Not Spring - Climate Drives Annual Adult Survival in Common Passerines: A Country-Wide, Multi-Species Modeling Exercise

Authors: Manon Ghislain, Timothée Bonnet, Olivier Gimenez, Olivier Dehorter, Pierre-Yves Henry

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Climatic fluctuations affect the demography of animal populations, generating changes in population size, phenology, distribution and community assemblages. However, very few studies have identified the underlying demographic processes. For short-lived species, like common passerine birds, are these changes generated by changes in adult survival or in fecundity and recruitment? This study tests for an effect of annual climatic conditions (spring and winter) on annual, local adult survival at very large spatial (a country, 252 sites), temporal (25 years) and biological (25 species) scales. The Constant Effort Site ringing has allowed the collection of capture - mark - recapture data for 100 000 adult individuals since 1989, over metropolitan France, thus documenting annual, local survival rates of the most common passerine birds. We specifically developed a set of multi-year, multi-species, multi-site Bayesian models describing variations in local survival and recapture probabilities. This method allows for a statistically powerful hierarchical assessment (global versus species-specific) of the effects of climate variables on survival. A major part of between-year variations in survival rate was common to all species (74% of between-year variance), whereas only 26% of temporal variation was species-specific. Although changing spring climate is commonly invoked as a cause of population size fluctuations, spring climatic anomalies (mean precipitation or temperature for March-August) do not impact adult survival: only 1% of between-year variation of species survival is explained by spring climatic anomalies. However, for sedentary birds, winter climatic anomalies (North Atlantic Oscillation) had a significant, quadratic effect on adult survival, birds surviving less during intermediate years than during more extreme years. For migratory birds, we do not detect an effect of winter climatic anomalies (Sahel Rainfall). We will analyze the life history traits (migration, habitat, thermal range) that could explain a different sensitivity of species to winter climate anomalies. Overall, we conclude that changes in population sizes for passerine birds are unlikely to be the consequences of climate-driven mortality (or emigration) in spring but could be induced by other demographic parameters, like fecundity.

Keywords: Bayesian approach, capture-recapture, climate anomaly, constant effort sites scheme, passerine, seasons, survival

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231 Transgenerational Impact of Intrauterine Hyperglycaemia to F2 Offspring without Pre-Diabetic Exposure on F1 Male Offspring

Authors: Jun Ren, Zhen-Hua Ming, He-Feng Huang, Jian-Zhong Sheng

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Adverse intrauterine stimulus during critical or sensitive periods in early life, may lead to health risk not only in later life span, but also further generations. Intrauterine hyperglycaemia, as a major feature of gestational diabetes mellitus (GDM), is a typical adverse environment for both F1 fetus and F1 gamete cells development. However, there is scare information of phenotypic difference of metabolic memory between somatic cells and germ cells exposed by intrauterine hyperglycaemia. The direct transmission effect of intrauterine hyperglycaemia per se has not been assessed either. In this study, we built a GDM mice model and selected male GDM offspring without pre-diabetic phenotype as our founders, to exclude postnatal diabetic influence on gametes, thereby investigate the direct transmission effect of intrauterine hyperglycaemia exposure on F2 offspring, and we further compared the metabolic difference of affected F1-GDM male offspring and F2 offspring. A GDM mouse model of intrauterine hyperglycemia was established by intraperitoneal injection of streptozotocin after pregnancy. Pups of GDM mother were fostered by normal control mothers. All the mice were fed with standard food. Male GDM offspring without metabolic dysfunction phenotype were crossed with normal female mice to obtain F2 offspring. Body weight, glucose tolerance test, insulin tolerance test and homeostasis model of insulin resistance (HOMA-IR) index were measured in both generations at 8 week of age. Some of F1-GDM male mice showed impaired glucose tolerance (p < 0.001), none of F1-GDM male mice showed impaired insulin sensitivity. Body weight of F1-GDM mice showed no significance with control mice. Some of F2-GDM offspring exhibited impaired glucose tolerance (p < 0.001), all the F2-GDM offspring exhibited higher HOMA-IR index (p < 0.01 of normal glucose tolerance individuals vs. control, p < 0.05 of glucose intolerance individuals vs. control). All the F2-GDM offspring exhibited higher ITT curve than control (p < 0.001 of normal glucose tolerance individuals, p < 0.05 of glucose intolerance individuals, vs. control). F2-GDM offspring had higher body weight than control mice (p < 0.001 of normal glucose tolerance individuals, p < 0.001 of glucose intolerance individuals, vs. control). While glucose intolerance is the only phenotype that F1-GDM male mice may exhibit, F2 male generation of healthy F1-GDM father showed insulin resistance, increased body weight and/or impaired glucose tolerance. These findings imply that intrauterine hyperglycaemia exposure affects germ cells and somatic cells differently, thus F1 and F2 offspring demonstrated distinct metabolic dysfunction phenotypes. And intrauterine hyperglycaemia exposure per se has a strong influence on F2 generation, independent of postnatal metabolic dysfunction exposure.

Keywords: inheritance, insulin resistance, intrauterine hyperglycaemia, offspring

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230 Model-Driven and Data-Driven Approaches for Crop Yield Prediction: Analysis and Comparison

Authors: Xiangtuo Chen, Paul-Henry Cournéde

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Crop yield prediction is a paramount issue in agriculture. The main idea of this paper is to find out efficient way to predict the yield of corn based meteorological records. The prediction models used in this paper can be classified into model-driven approaches and data-driven approaches, according to the different modeling methodologies. The model-driven approaches are based on crop mechanistic modeling. They describe crop growth in interaction with their environment as dynamical systems. But the calibration process of the dynamic system comes up with much difficulty, because it turns out to be a multidimensional non-convex optimization problem. An original contribution of this paper is to propose a statistical methodology, Multi-Scenarios Parameters Estimation (MSPE), for the parametrization of potentially complex mechanistic models from a new type of datasets (climatic data, final yield in many situations). It is tested with CORNFLO, a crop model for maize growth. On the other hand, the data-driven approach for yield prediction is free of the complex biophysical process. But it has some strict requirements about the dataset. A second contribution of the paper is the comparison of these model-driven methods with classical data-driven methods. For this purpose, we consider two classes of regression methods, methods derived from linear regression (Ridge and Lasso Regression, Principal Components Regression or Partial Least Squares Regression) and machine learning methods (Random Forest, k-Nearest Neighbor, Artificial Neural Network and SVM regression). The dataset consists of 720 records of corn yield at county scale provided by the United States Department of Agriculture (USDA) and the associated climatic data. A 5-folds cross-validation process and two accuracy metrics: root mean square error of prediction(RMSEP), mean absolute error of prediction(MAEP) were used to evaluate the crop prediction capacity. The results show that among the data-driven approaches, Random Forest is the most robust and generally achieves the best prediction error (MAEP 4.27%). It also outperforms our model-driven approach (MAEP 6.11%). However, the method to calibrate the mechanistic model from dataset easy to access offers several side-perspectives. The mechanistic model can potentially help to underline the stresses suffered by the crop or to identify the biological parameters of interest for breeding purposes. For this reason, an interesting perspective is to combine these two types of approaches.

Keywords: crop yield prediction, crop model, sensitivity analysis, paramater estimation, particle swarm optimization, random forest

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229 Predicting Polyethylene Processing Properties Based on Reaction Conditions via a Coupled Kinetic, Stochastic and Rheological Modelling Approach

Authors: Kristina Pflug, Markus Busch

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Being able to predict polymer properties and processing behavior based on the applied operating reaction conditions in one of the key challenges in modern polymer reaction engineering. Especially, for cost-intensive processes such as the high-pressure polymerization of low-density polyethylene (LDPE) with high safety-requirements, the need for simulation-based process optimization and product design is high. A multi-scale modelling approach was set-up and validated via a series of high-pressure mini-plant autoclave reactor experiments. The approach starts with the numerical modelling of the complex reaction network of the LDPE polymerization taking into consideration the actual reaction conditions. While this gives average product properties, the complex polymeric microstructure including random short- and long-chain branching is calculated via a hybrid Monte Carlo-approach. Finally, the processing behavior of LDPE -its melt flow behavior- is determined in dependence of the previously determined polymeric microstructure using the branch on branch algorithm for randomly branched polymer systems. All three steps of the multi-scale modelling approach can be independently validated against analytical data. A triple-detector GPC containing an IR, viscosimetry and multi-angle light scattering detector is applied. It serves to determine molecular weight distributions as well as chain-length dependent short- and long-chain branching frequencies. 13C-NMR measurements give average branching frequencies, and rheological measurements in shear and extension serve to characterize the polymeric flow behavior. The accordance of experimental and modelled results was found to be extraordinary, especially taking into consideration that the applied multi-scale modelling approach does not contain parameter fitting of the data. This validates the suggested approach and proves its universality at the same time. In the next step, the modelling approach can be applied to other reactor types, such as tubular reactors or industrial scale. Moreover, sensitivity analysis for systematically varying process conditions is easily feasible. The developed multi-scale modelling approach finally gives the opportunity to predict and design LDPE processing behavior simply based on process conditions such as feed streams and inlet temperatures and pressures.

Keywords: low-density polyethylene, multi-scale modelling, polymer properties, reaction engineering, rheology

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228 European Hinterland and Foreland: Impact of Accessibility, Connectivity, Inter-Port Competition on Containerization

Authors: Dial Tassadit Rania, Figueiredo De Oliveira Gabriel

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In this paper, we investigate the relationship between ports and their hinterland and foreland environments and the competitive relationship between the ports themselves. These two environments are changing, evolving and introducing new challenges for commercial and economic development at the regional, national and international levels. Because of the rise of the containerization phenomenon, shipping costs and port handling costs have considerably decreased due to economies of scale. The volume of maritime trade has increased substantially and the markets served by the ports have expanded. On these bases, overlapping hinterlands can give rise to the phenomenon of competition between ports. Our main contribution comparing to the existing literature on this issue, is to build a set of hinterland, foreland and competition indicators. Using these indicators? we investigate the effect of hinterland accessibility, foreland connectivity and inter-ports competition on containerized traffic of Europeans ports. For this, we have a 10-year panel database from 2004 to 2014. Our hinterland indicators are given by two indicators of accessibility; they describe the market potential of a port and are calculated using information on population and wealth (GDP). We then calculate population and wealth for different neighborhoods within a distance from a port ranging from 100 to 1000km. For the foreland, we produce two indicators: port connectivity and number of partners for each port. Finally, we compute the two indicators of inter-port competition and a market concentration indicator (Hirshmann-Herfindhal) for different neighborhood-distances around the port. We then apply a fixed-effect model to test the relationship above. Again, with a fixed effects model, we do a sensitivity analysis for each of these indicators to support the results obtained. The econometric results of the general model given by the regression of the accessibility indicators, the LSCI for port i, and the inter-port competition indicator on the containerized traffic of European ports show a positive and significant effect for accessibility to wealth and not to the population. The results are positive and significant for the two indicators of connectivity and competition as well. One of the main results of this research is that the port development given here by the increase of its containerized traffic is strongly related to the development of its hinterland and foreland environment. In addition, it is the market potential, given by the wealth of the hinterland that has an impact on the containerized traffic of a port. However, accessibility to a large population pool is not important for understanding the dynamics of containerized port traffic. Furthermore, in order to continue to develop, a port must penetrate its hinterland at a deep level exceeding 100 km around the port and seek markets beyond this perimeter. The port authorities could focus their marketing efforts on the immediate hinterland, which can, as the results shows, not be captive and thus engage new approaches of port governance to make it more attractive.

Keywords: accessibility, connectivity, European containerization, European hinterland and foreland, inter-port competition

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227 Management of Caverno-Venous Leakage: A Series of 133 Patients with Symptoms, Hemodynamic Workup, and Results of Surgery

Authors: Allaire Eric, Hauet Pascal, Floresco Jean, Beley Sebastien, Sussman Helene, Virag Ronald

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Background: Caverno-venous leakage (CVL) is devastating, although barely known disease, the first cause of major physical impairment in men under 25, and responsible for 50% of resistances to phosphodiesterase 5-inhibitors (PDE5-I), affecting 30 to 40% of users in this medication class. In this condition, too early blood drainage from corpora cavernosa prevents penile rigidity and penetration during sexual intercourse. The role of conservative surgery in this disease remains controversial. Aim: Assess complications and results of combined open surgery and embolization for CVL. Method: Between June 2016 and September 2021, 133 consecutive patients underwent surgery in our institution for CVL, causing severe erectile dysfunction (ED) resistance to oral medical treatment. Procedures combined vein embolization and ligation with microsurgical techniques. We performed a pre-and post-operative clinical (Erection Harness Scale: EHS) hemodynamic evaluation by duplex sonography in all patients. Before surgery, the CVL network was visualized by computed tomography cavernography. Penile EMG was performed in case of diabetes or suspected other neurological conditions. All patients were optimized for hormonal status—data we prospectively recorded. Results: Clinical signs suggesting CVL were ED since age lower than 25, loss of erection when changing position, penile rigidity varying according to the position. Main complications were minor pulmonary embolism in 2 patients, one after airline travel, one with Factor V Leiden heterozygote mutation, one infection and three hematomas requiring reoperation, one decreased gland sensitivity lasting for more than one year. Mean pre-operative pharmacologic EHS was 2.37+/-0.64, mean pharmacologic post-operative EHS was 3.21+/-0.60, p<0.0001 (paired t-test). The mean EHS variation was 0.87+/-0.74. After surgery, 81.5% of patients had a pharmacologic EHS equal to or over 3, allowing for intercourse with penetration. Three patients (2.2%) experienced lower post-operative EHS. The main cause of failure was leakage from the deep dorsal aspect of the corpus cavernosa. In a 14 months follow-up, 83.2% of patients had a clinical EHS equal to or over 3, allowing for sexual intercourse with penetration, one-third of them without any medication. 5 patients had a penile implant after unsuccessful conservative surgery. Conclusion: Open surgery combined with embolization for CVL is an efficient approach to CVL causing severe erectile dysfunction.

Keywords: erectile dysfunction, cavernovenous leakage, surgery, embolization, treatment, result, complications, penile duplex sonography

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226 Occult Haemolacria Paradigm in the Study of Tears

Authors: Yuliya Huseva

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To investigate the contents of tears to determine latent blood. Methods: Tear samples from 72 women were studied with the microscopy of tears aspirated with a capillary and stained by Nocht and with a chemical method of test strips with chromogen. Statistical data processing was carried out using statistical packages Statistica 10.0 for Windows, calculation of Pearson's chi-square test, Yule association coefficient, the method of determining sensitivity and specificity. Results:, In 30.6% (22) of tear samples erythrocytes were revealed microscopically. Correlations between the presence of erythrocytes in the tear and the phase of the menstrual cycle has been discovered. In the follicular phase of the cycle, erythrocytes were found in 59.1% (13) people, which is significantly more (x2=4.2, p=0.041) compared to the luteal phase - in 40.9% (9) women. In the first seven days of the follicular phase of the menstrual cycle the erythrocytes were predominanted of in the tears of women examined testifies in favour of the vicarious bleeding from the mucous membranes of extragenital organs in sync with menstruation. Of the other cellular elements in tear samples with latent haemolacria, neutrophils prevailed - in 45.5% (10), while lymphocytes were less common - in 27.3% (6), because neutrophil exudation is accompanied by vasodilatation of the conjunctiva and the release of erythrocytes into the conjunctival cavity. It was found that the prognostic significance of the chemical method was 0.53 of the microscopic method. In contrast to microscopy, which detected blood in tear samples from 30.6% (22) of women, blood was detected chemically in tears of 16.7% (12). An association between latent haemolacria and endometriosis was found (k=0.75, p≤0.05). Microscopically, in the tears of patients with endometriosis, erythrocytes were detected in 70% of cases, while in healthy women without endometriosis - in 25% of cases. The proportion of women with erythrocytes in tears, determined by a chemical method, was 41.7% among patients with endometriosis, which is significantly more (x2=6.5, p=0.011) than 11.7% among women without endometriosis. The data obtained can be explained by the etiopathogenesis of the extragenital endometriosis which is caused by hematogenous spread of endometrial tissue into the orbit. In endometriosis, erythrocytes are found against the background of accumulations of epithelial cells. In the tear samples of 4 women with endometriosis, glandular cuboidal epithelial cells, morphologically similar to endometrial cells, were found, which may indicate a generalization of the disease. Conclusions: Single erythrocytes can normally be found in the tears, their number depends on the phase of the menstrual cycle, increasing in the follicular phase. Erythrocytes found in tears against the background of accumulations of epitheliocytes and their glandular atypia may indicate a manifestation of extragenital endometriosis. Both used methods (microscopic and chemical) are informative in revealing latent haemolacria. The microscopic method is more sensitive, reveals intact erythrocytes, and besides, it provides information about other cells. At the same time, the chemical method is faster and technically simpler, it determines the presence of haemoglobin and its metabolic products, and can be used as a screening.

Keywords: tear, blood, microscopy, epitheliocytes

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225 In the Primary Education, the Classroom Teacher's Procedure of Coping WITH Stress, the Health of Psyche and the Direction of Check Point

Authors: Caglayan Pinar Demirtas, Mustafa Koc

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Objective: This study was carried out in order to find out; the methods which are used by primary school teachers to cope with stress, their psychological health, and the direction of controlling focus. The study was carried out by using the ‘school survey’ and ‘society survey’ methods. Method: The study included primary school teachers. The study group was made up of 1066 people; 511 women and 555 men who accepted volunteerly to complete; ‘the inventory for collecting data, ‘the Scale for Attitude of Overcoming Stress’ (SBTE / SAOS), ‘Rotter’s Scale for the Focus of Inner- Outer Control’ (RİDKOÖ / RSFIOC), and ‘the Symptom Checking List’ (SCL- 90). The data was collected by using ‘the Scale for Attitude of Overcoming Stress’, ‘the Scale for the Focus of Inner- Outer Control’, ‘the Symptom Checking List’, and a personal information form developed by the researcher. SPSS for Windows packet programme was used. Result: The age variable is a factor in interpersonal sensitivity, depression, anxciety, hostality symptoms but it is not a factor in the other symptoms. The variable, gender, is a factor in emotional practical escaping overcoming method but it is not a factor in the other overcoming methods. Namely, it has been found out that, women use emotional practical escaping overcoming method more than men. Marital status is a factor in methods of overcoming stress such as trusting in religion, emotional practical escaping and biochemical escaping while it is not a factor in the other methods. Namely, it has been found out that married teachers use trusting in religion method, and emotional practical escaping method more than single ones. Single teachers generally use biochemical escaping method. In primary school teachers’ direction of controlling focus, gender variable is a factor. It has been found out that women are more inner controlled while the men are more outer controlled. The variable, time of service, is a factor in the direction of controlling focus; that is, teachers with 1-5 years of service time are more inner controlled compared with teachers with 16-20 years of service time. The variable, age, is a factor in the direction of controlling focus; that is, teachers in 26-30 age groups are more outer controlled compared with the other age groups and again teachers in 26-30 age group are more inner controlled when compared with the other age groups. Direction of controlling focus is a factor in the primary school teachers’ psychological health. Namely, being outer controlled is a factor but being inner controlled is not. The methods; trusting in religion, active plannıng and biochemical escaping used by primary school teachers to cope with stress act as factors in the direction of controlling focus but not in the others. Namely, it has been found out that outer controlled teachers prefer the methods of trusting in religion and active planning while the inner controlled ones prefer biochemical escaping.

Keywords: coping with, controlling focus, psychological health, stress

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224 Investigating Early Markers of Alzheimer’s Disease Using a Combination of Cognitive Tests and MRI to Probe Changes in Hippocampal Anatomy and Functionality

Authors: Netasha Shaikh, Bryony Wood, Demitra Tsivos, Michael Knight, Risto Kauppinen, Elizabeth Coulthard

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Background: Effective treatment of dementia will require early diagnosis, before significant brain damage has accumulated. Memory loss is an early symptom of Alzheimer’s disease (AD). The hippocampus, a brain area critical for memory, degenerates early in the course of AD. The hippocampus comprises several subfields. In contrast to healthy aging where CA3 and dentate gyrus are the hippocampal subfields with most prominent atrophy, in AD the CA1 and subiculum are thought to be affected early. Conventional clinical structural neuroimaging is not sufficiently sensitive to identify preferential atrophy in individual subfields. Here, we will explore the sensitivity of new magnetic resonance imaging (MRI) sequences designed to interrogate medial temporal regions as an early marker of Alzheimer’s. As it is likely a combination of tests may predict early Alzheimer’s disease (AD) better than any single test, we look at the potential efficacy of such imaging alone and in combination with standard and novel cognitive tasks of hippocampal dependent memory. Methods: 20 patients with mild cognitive impairment (MCI), 20 with mild-moderate AD and 20 age-matched healthy elderly controls (HC) are being recruited to undergo 3T MRI (with sequences designed to allow volumetric analysis of hippocampal subfields) and a battery of cognitive tasks (including Paired Associative Learning from CANTAB, Hopkins Verbal Learning Test and a novel hippocampal-dependent abstract word memory task). AD participants and healthy controls are being tested just once whereas patients with MCI will be tested twice a year apart. We will compare subfield size between groups and correlate subfield size with cognitive performance on our tasks. In the MCI group, we will explore the relationship between subfield volume, cognitive test performance and deterioration in clinical condition over a year. Results: Preliminary data (currently on 16 participants: 2 AD; 4 MCI; 9 HC) have revealed subfield size differences between subject groups. Patients with AD perform with less accuracy on tasks of hippocampal-dependent memory, and MCI patient performance and reaction times also differ from healthy controls. With further testing, we hope to delineate how subfield-specific atrophy corresponds with changes in cognitive function, and characterise how this progresses over the time course of the disease. Conclusion: Novel sequences on a MRI scanner such as those in route in clinical use can be used to delineate hippocampal subfields in patients with and without dementia. Preliminary data suggest that such subfield analysis, perhaps in combination with cognitive tasks, may be an early marker of AD.

Keywords: Alzheimer's disease, dementia, memory, cognition, hippocampus

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223 Role of Indigenous Peoples in Climate Change

Authors: Neelam Kadyan, Pratima Ranga, Yogender

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Indigenous people are the One who are affected by the climate change the most, although there have contributed little to its causes. This is largely a result of their historic dependence on local biological diversity, ecosystem services and cultural landscapes as a source of their sustenance and well-being. Comprising only four percent of the world’s population they utilize 22 percent of the world’s land surface. Despite their high exposure-sensitivity indigenous peoples and local communities are actively responding to changing climatic conditions and have demonstrated their resourcefulness and resilience in the face of climate change. Traditional Indigenous territories encompass up to 22 percent of the world’s land surface and they coincide with areas that hold 80 percent of the planet’s biodiversity. Also, the greatest diversity of indigenous groups coincides with the world’s largest tropical forest wilderness areas in the Americas (including Amazon), Africa, and Asia, and 11 percent of world forest lands are legally owned by Indigenous Peoples and communities. This convergence of biodiversity-significant areas and indigenous territories presents an enormous opportunity to expand efforts to conserve biodiversity beyond parks, which tend to benefit from most of the funding for biodiversity conservation. Tapping on Ancestral Knowledge Indigenous Peoples are carriers of ancestral knowledge and wisdom about this biodiversity. Their effective participation in biodiversity conservation programs as experts in protecting and managing biodiversity and natural resources would result in more comprehensive and cost effective conservation and management of biodiversity worldwide. Addressing the Climate Change Agenda Indigenous Peoples has played a key role in climate change mitigation and adaptation. The territories of indigenous groups who have been given the rights to their lands have been better conserved than the adjacent lands (i.e., Brazil, Colombia, Nicaragua, etc.). Preserving large extensions of forests would not only support the climate change objectives, but it would respect the rights of Indigenous Peoples and conserve biodiversity as well. A climate change agenda fully involving Indigenous Peoples has many more benefits than if only government and/or the private sector are involved. Indigenous peoples are some of the most vulnerable groups to the negative effects of climate change. Also, they are a source of knowledge to the many solutions that will be needed to avoid or ameliorate those effects. For example, ancestral territories often provide excellent examples of a landscape design that can resist the negatives effects of climate change. Over the millennia, Indigenous Peoples have developed adaptation models to climate change. They have also developed genetic varieties of medicinal and useful plants and animal breeds with a wider natural range of resistance to climatic and ecological variability.

Keywords: ancestral knowledge, cost effective conservation, management, indigenous peoples, climate change

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222 Forecasting Residential Water Consumption in Hamilton, New Zealand

Authors: Farnaz Farhangi

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Many people in New Zealand believe that the access to water is inexhaustible, and it comes from a history of virtually unrestricted access to it. For the region like Hamilton which is one of New Zealand’s fastest growing cities, it is crucial for policy makers to know about the future water consumption and implementation of rules and regulation such as universal water metering. Hamilton residents use water freely and they do not have any idea about how much water they use. Hence, one of proposed objectives of this research is focusing on forecasting water consumption using different methods. Residential water consumption time series exhibits seasonal and trend variations. Seasonality is the pattern caused by repeating events such as weather conditions in summer and winter, public holidays, etc. The problem with this seasonal fluctuation is that, it dominates other time series components and makes difficulties in determining other variations (such as educational campaign’s effect, regulation, etc.) in time series. Apart from seasonality, a stochastic trend is also combined with seasonality and makes different effects on results of forecasting. According to the forecasting literature, preprocessing (de-trending and de-seasonalization) is essential to have more performed forecasting results, while some other researchers mention that seasonally non-adjusted data should be used. Hence, I answer the question that is pre-processing essential? A wide range of forecasting methods exists with different pros and cons. In this research, I apply double seasonal ARIMA and Artificial Neural Network (ANN), considering diverse elements such as seasonality and calendar effects (public and school holidays) and combine their results to find the best predicted values. My hypothesis is the examination the results of combined method (hybrid model) and individual methods and comparing the accuracy and robustness. In order to use ARIMA, the data should be stationary. Also, ANN has successful forecasting applications in terms of forecasting seasonal and trend time series. Using a hybrid model is a way to improve the accuracy of the methods. Due to the fact that water demand is dominated by different seasonality, in order to find their sensitivity to weather conditions or calendar effects or other seasonal patterns, I combine different methods. The advantage of this combination is reduction of errors by averaging of each individual model. It is also useful when we are not sure about the accuracy of each forecasting model and it can ease the problem of model selection. Using daily residential water consumption data from January 2000 to July 2015 in Hamilton, I indicate how prediction by different methods varies. ANN has more accurate forecasting results than other method and preprocessing is essential when we use seasonal time series. Using hybrid model reduces forecasting average errors and increases the performance.

Keywords: artificial neural network (ANN), double seasonal ARIMA, forecasting, hybrid model

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221 Assessment of Physical Activity and Sun Exposure of Saudi Patients with Type 2 Diabetes Mellitus in Ramadan and Non-Ramadan Periods

Authors: Abdullah S. Alghamdi, Khaled Alghamdi, Richard O. Jenkins, Parvez I. Haris

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Background: Physical activity is an important factor in the treatment and prevention of type 2 diabetes mellitus (T2DM). Reduction in HbA1c level, an important diabetes biomarker, was reported in patients who increased their daily physical activity. Although the ambient temperature was reported to be positively correlated to a negative impact on health and increase the incidences of diabetes, the exposure to bright sunlight was recently found to be associated with enhanced insulin sensitivity and improved beta-cell function. How Ramadan alters physical activity, and especially sunlight exposure, has not been adequately investigated. Aim: This study aimed to assess the physical activity and sun exposure of Saudis with T2DM over different periods (before, during, and after Ramadan) and related this to HbA1c levels. Methods: This study recruited 82 Saudis with T2DM, who chose to fast during Ramadan, from the Endocrine and Diabetic Centre of Al Iman General Hospital, Riyadh, Saudi Arabia. Ethical approvals for this study were obtained from De Montfort University and Saudi Ministry of Health. Physical activity and sun exposure were assessed by a self-administered questionnaire. Physical activity was estimated using the International Physical Activity Questionnaire (IPAQ), while the sun exposure was assessed by asking the patients about their hours per week of direct exposure to the sun, and daily hours spent outdoors. Blood samples were collected in each period for measuring HbA1c. Results: Low physical activity was observed in more than 60% of the patients, with no significant changes between periods. There were no significant variances between periods in the daily hours spent outdoors and the total number of weekly hours of direct exposure to the sun. The majority of patients reported only few hours of exposure to the sun (1h or less per week) and time spent outdoors (1h or less per day). The mean HbA1c significantly changed between periods (P = 0.001), with lowest level during Ramadan. There were significant differences in the mean HbA1c between the groups for the level of physical activity (P < 0.001), with significant lower mean HbA1c in the higher-level group. There were no significant variances in the mean of HbA1c between the groups for the daily hours spent outdoors. The mean HbA1c of the patients, who reported never in their total weekly hours of exposure to the sun, was significantly lower than the mean HbA1c of those who reported 1 hour or less (P = 0.001). Conclusion: Physical inactivity was prevalent among the study population with very little exposure to the sun or time spent outdoors. Higher level of physical activity was associated with lower mean HbA1c levels. Encouraging T2DM patients to achieve the recommended levels of physical activity may help them to obtain greater benefits of Ramadan fasting, such as reducing their HbA1c levels. The impact of low direct exposure to the sun and the time spent outdoors needs to be further investigated in both healthy and diabetic patients.

Keywords: diabetes, fasting, physical activity, sunlight, Ramadan

Procedia PDF Downloads 160
220 Gender Policies and Political Culture: An Examination of the Canadian Context

Authors: Chantal Maille

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This paper is about gender-based analysis plus (GBA+), an intersectional gender policy used in Canada to assess the impact of policies and programs for men and women from different origins. It looks at Canada’s political culture to explain the nature of its gender policies. GBA+ is defined as an analysis method that makes it possible to assess the eventual effects of policies, programs, services, and other initiatives on women and men of different backgrounds because it takes account of gender and other identity factors. The ‘plus’ in the name serves to emphasize that GBA+ goes beyond gender to include an examination of a wide range of other related identity factors, such as age, education, language, geography, culture, and income. The point of departure for GBA+ is that women and men are not homogeneous populations and gender is never the only factor in defining a person’s identity; rather, it interacts with factors such as ethnic origin, age, disabilities, where the person lives, and other aspects of individual and social identity. GBA+ takes account of these factors and thus challenges notions of similarity or homogeneity within populations of women and men. Comparative analysis based on sex and gender may serve as a gateway to studying a given question, but women, men, girls, and boys do not form homogeneous populations. In the 1990s, intersectionality emerged as a new feminist framework. The popularity of the notion of intersectionality corresponds to a time when, in hindsight, the damage done to minoritized groups by state disengagement policies in concert with global intensification of neoliberalism, and vice versa, can be measured. Although GBA+ constitutes a form of intersectionalization of GBA, it must be understood that the two frameworks do not spring from a similar logic. Intersectionality first emerged as a dynamic analysis of differences between women that was oriented toward change and social justice, whereas GBA is a technique developed by state feminists in a context of analyzing governmental policies and aiming to promote equality between men and women. It can nevertheless be assumed that there might be interest in such a policy and program analysis grid that is decentred from gender and offers enough flexibility to take account of a group of inequalities. In terms of methodology, the research is supported by a qualitative analysis of governmental documents about GBA+ in Canada. Research findings identify links between Canadian gender policies and its political culture. In Canada, diversity has been taken into account as an element at the basis of gendered analysis of public policies since 1995. The GBA+ adopted by the government of Canada conveys an opening to intersectionality and a sensitivity to multiculturalism. The Canadian Multiculturalism Act, adopted 1988, proposes to recognize the fact that multiculturalism is a fundamental characteristic of the Canadian identity and heritage and constitutes an invaluable resource for the future of the country. In conclusion, Canada’s distinct political culture can be associated with the specific nature of its gender policies.

Keywords: Canada, gender-based analysis, gender policies, political culture

Procedia PDF Downloads 222
219 Bi-objective Network Optimization in Disaster Relief Logistics

Authors: Katharina Eberhardt, Florian Klaus Kaiser, Frank Schultmann

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Last-mile distribution is one of the most critical parts of a disaster relief operation. Various uncertainties, such as infrastructure conditions, resource availability, and fluctuating beneficiary demand, render last-mile distribution challenging in disaster relief operations. The need to balance critical performance criteria like response time, meeting demand and cost-effectiveness further complicates the task. The occurrence of disasters cannot be controlled, and the magnitude is often challenging to assess. In summary, these uncertainties create a need for additional flexibility, agility, and preparedness in logistics operations. As a result, strategic planning and efficient network design are critical for an effective and efficient response. Furthermore, the increasing frequency of disasters and the rising cost of logistical operations amplify the need to provide robust and resilient solutions in this area. Therefore, we formulate a scenario-based bi-objective optimization model that integrates pre-positioning, allocation, and distribution of relief supplies extending the general form of a covering location problem. The proposed model aims to minimize underlying logistics costs while maximizing demand coverage. Using a set of disruption scenarios, the model allows decision-makers to identify optimal network solutions to address the risk of disruptions. We provide an empirical case study of the public authorities’ emergency food storage strategy in Germany to illustrate the potential applicability of the model and provide implications for decision-makers in a real-world setting. Also, we conduct a sensitivity analysis focusing on the impact of varying stockpile capacities, single-site outages, and limited transportation capacities on the objective value. The results show that the stockpiling strategy needs to be consistent with the optimal number of depots and inventory based on minimizing costs and maximizing demand satisfaction. The strategy has the potential for optimization, as network coverage is insufficient and relies on very high transportation and personnel capacity levels. As such, the model provides decision support for public authorities to determine an efficient stockpiling strategy and distribution network and provides recommendations for increased resilience. However, certain factors have yet to be considered in this study and should be addressed in future works, such as additional network constraints and heuristic algorithms.

Keywords: humanitarian logistics, bi-objective optimization, pre-positioning, last mile distribution, decision support, disaster relief networks

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218 Characterization of the Lytic Bacteriophage VbɸAB-1 against Drug Resistant Acinetobacter baumannii Isolated from Hospitalized Pressure Ulcers Patients

Authors: M. Doudi, M. H. Pazandeh, L. Rahimzadeh Torabi

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Bedsores are pressure ulcers that occur on the skin or tissue due to being immobile and lying in bed for extended periods. Bedsores have the potential to progress into open ulcers, increasing the possibility of variety of bacterial infection. Acinetobacter baumannii, a pathogen of considerable clinical importance, exhibited a significant correlation with Bedsores (pressure ulcers) infections, thereby manifesting a wide spectrum of antibiotic resistance. The emergence of drug resistance has led researchers to focus on alternative methods, particularly phage therapy, for tackling bacterial infections. Phage therapy has emerged as a novel therapeutic approach to regulate the activity of these agents. The management of bacterial infections greatly benefits from the clinical utilization of bacteriophages as a valuable antimicrobial intervention. The primary objective of this investigation consisted of isolating and discerning potent bacteriophage capable of targeting multi drug-resistant (MDR) and extensively drug-resistant (XDR) bacteria obtained from pressure ulcers. In present study, analyzed and isolated A. baumannii strains obtained from a cohort of patients suffering from pressure ulcers at Taleghani Hospital in Ahvaz, Iran. An approach that included biochemical and molecular identification techniques was used to determine the taxonomic classification of bacterial isolates at the genus and species levels. The molecular identification process was facilitated by using the 16S rRNA gene in combination with universal primers 27 F, and 1492 R. Bacteriophage was obtained through the isolation process conducted on treatment plant sewage located in Isfahan, Iran. The main goal of this study was to evaluate different characteristics of phage, such as their appearance, range of hosts they can infect, how quickly they can enter a host, their stability at varying temperatures and pH levels, their effectiveness in killing bacteria, the growth pattern of a single phage stage, mapping of enzymatic digestion, and identification of proteomics patterns. The findings demonstrated that an examination was conducted on a sample of 50 specimens, wherein 15 instances of A. baumannii were identified. These microorganisms are the predominant Gram-negative agents known to cause wound infections in individuals suffering from bedsores. The study's findings indicated a high prevalence of antibiotic resistance in the strains isolated from pressure ulcers, excluding the clinical strains that exhibited responsiveness to colistin.According to the findings obtained from assessments of host range and morphological characteristics of bacteriophage VbɸAB-1, it can be concluded that this phage possesses specificity towards A. Baumannii BAH_Glau1001 was classified as a member of the Plasmaviridae family. The bacteriophage mentioned earlier showed the strongest antibacterial effect at a temperature of 18 °C and a pH of 6.5. Through the utilization of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis on protein fragments, it was established that the bacteriophage VbɸAB-1 exhibited a size range between 50 and 75 kilodaltons (KDa). The numerous research findings on the effectiveness of phages and the safety studies conducted suggest that the phages studied in this research can be considered as a practical solution and recommended approach for controlling and treating stubborn pathogens in burn wounds among hospitalized patients.

Keywords: acinetobacter baumannii, extremely drug- resistant, phage therapy, surgery wound

Procedia PDF Downloads 92
217 Evolutionary Analysis of Influenza A (H1N1) Pdm 09 in Post Pandemic Period in Pakistan

Authors: Nazish Badar

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In early 2009, Pandemic type A (H1N1) Influenza virus emerged globally. Since then, it has continued circulation causing considerable morbidity and mortality. The purpose of this study was to evaluate the evolutionary changes in Influenza A (H1N1) pdm09 viruses from 2009-15 and their relevance with the current vaccine viruses. Methods: Respiratory specimens were collected with influenza-like illness and Severe Acute Respiratory Illness. Samples were processed according to CDC protocol. Sequencing and phylogenetic analysis of Haemagglutinin (HA) and neuraminidase (NA) genes was carried out comparing representative isolates from Pakistan viruses. Results: Between Jan2009 - Feb 2016, 1870 (13.2%) samples were positive for influenza A out of 14086. During the pandemic period (2009–10), Influenza A/ H1N1pdm 09 was the dominant strain with 366 (45%) of total influenza positives. In the post-pandemic period (2011–2016), a total of 1066 (59.6%) cases were positive Influenza A/ H1N1pdm 09 with co-circulation of different Influenza A subtypes. Overall, the Pakistan A(H1N1) pdm09 viruses grouped in two genetic clades. Influenza A(H1N1)pdm09 viruses only ascribed to Clade 7 during the pandemic period whereas viruses belong to clade 7 (2011) and clade 6B (2015) during the post-pandemic years. Amino acid analysis of the HA gene revealed mutations at positions S220T, I338V and P100S specially associated with outbreaks in all the analyzed strains. Sequence analyses of post-pandemic A(H1N1)pdm09 viruses showed additional substitutions at antigenic sites; S179N,K180Q (SA), D185N, D239G (CA), S202A (SB) and at receptor binding sites; A13T, S200P when compared with pandemic period. Substitution at Genetic markers; A273T (69%), S200P/T (15%) and D239G (7.6%) associated with severity and E391K (69%) associated with virulence was identified in viruses isolated during 2015. Analysis of NA gene revealed outbreak markers; V106I (23%) among pandemic and N248D (100%) during post-pandemic Pakistan viruses. Additional N-Glycosylation site; HA S179N (23%), NA I23T(7.6%) and N44S (77%) in place of N386K(77%) were only found in post-pandemic viruses. All isolates showed histidine (H) at position 275 in NA indicating sensitivity to neuraminidase inhibitors. Conclusion: This study shows that the Influenza A(H1N1)pdm09 viruses from Pakistan clustered into two genetic clades, with co-circulation of some variants. Certain key substitutions in the receptor binding site and few changes indicative of virulence were also detected in post-pandemic strains. Therefore, it is imperative to continue monitoring of the viruses for early identification of potential variants of high virulence or emergence of drug-resistant variants.

Keywords: Influenza A (H1N1) pdm09, evolutionary analysis, post pandemic period, Pakistan

Procedia PDF Downloads 207
216 Coping with Incompatible Identities in Russia: Case of Orthodox Gays

Authors: Siuzan Uorner

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The era of late modernity is characterized, on the one hand, by social disintegration, values of personal freedom, tolerance, and self-expression. Boundaries between the accessible and the elitist, normal and abnormal are blurring. On the other hand, traditional social institutions, such as religion (especially Russian Orthodox Church), exist, criticizing lifestyle and worldview other than conventionally structured canons. Despite the declared values and opportunities in late modern society, people's freedom is ambivalent. Personal identity and its aspects are becoming a subject of choice. Hence, combinations of identity aspects can be incompatible. Our theoretical framework is based on P. Ricoeur's concept of narrative identity and hermeneutics, E. Goffman’s theory of social stigma, self-presentation, discrepant roles and W. James lectures about varieties of religious experience. This paper aims to reconstruct ways of coping with incompatible identities of Orthodox gays (an extreme sampling of a combination of sexual orientation and religious identity in a heteronormative society). This study focuses on the discourse of Orthodox gay parishioners and ROC gay priests in Russia (sampling ‘hard to reach’ populations because of the secrecy of gay community in ROC and sensitivity of the topic itself). We conducted a qualitative research design, using in-depth personal semi-structured online-interviews. Recruiting of informants took place in 'Nuntiare et Recreare' (Russian movement of religious LGBT) page in VKontakte through the post with an invitation to participate in the research. In this work, we analyzed interview transcripts using axial coding. We chose the Grounded Theory methodology to construct a theory from empirical data and contribute to the growing body of knowledge in ways of harmonizing incompatible identities in late modern societies. The research has found that there are two types of conflicts Orthodox gays meet with: canonic contradictions (postulates of Scripture and its interpretations) and problems in social interaction, mainly with ROC priests and Orthodox parishioners. We have revealed semantic meanings of most commonly used words that appear in the narratives (words such as ‘love’, ‘sin’, ‘religion’ etc.). Finally, we have reconstructed biographical patterns of LGBT social movements’ involvement. This paper argues that all incompatibilities are harmonizing in the narrative itself. As Ricoeur has suggested, the narrative configuration allows the speaker to gather facts and events together and to compose causal relationships between them. Sexual orientation and religious identity are getting along and harmonizing in the narrative.

Keywords: gay priests, incompatible identities, narrative identity, Orthodox gays, religious identity, ROC, sexual orientation

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215 Strategic Interventions to Combat Socio-economic Impacts of Drought in Thar - A Case Study of Nagarparkar

Authors: Anila Hayat

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Pakistan is one of those developing countries that are least involved in emissions but has the most vulnerable environmental conditions. Pakistan is ranked 8th in most affected countries by climate change on the climate risk index 1992-2011. Pakistan is facing severe water shortages and flooding as a result of changes in rainfall patterns, specifically in the least developed areas such as Tharparkar. Nagarparkar, once an attractive tourist spot located in Tharparkar because of its tropical desert climate, is now facing severe drought conditions for the last few decades. This study investigates the present socio-economic situation of local communities, major impacts of droughts and their underlying causes and current mitigation strategies adopted by local communities. The study uses both secondary (quantitative in nature) and primary (qualitative in nature) methods to understand the impacts and explore causes on the socio-economic life of local communities of the study area. The relevant data has been collected through household surveys using structured questionnaires, focus groups and in-depth interviews of key personnel from local and international NGOs to explore the sensitivity of impacts and adaptation to droughts in the study area. This investigation is limited to four rural communities of union council Pilu of Nagarparkar district, including Bheel, BhojaBhoon, Mohd Rahan Ji Dhani and Yaqub Ji Dhani villages. The results indicate that drought has caused significant economic and social hardships for the local communities as more than 60% of the overall population is dependent on rainfall which has been disturbed by irregular rainfall patterns. The decline in Crop yields has forced the local community to migrate to nearby areas in search of livelihood opportunities. Communities have not undertaken any appropriate adaptive actions to counteract the adverse effect of drought; they are completely dependent on support from the government and external aid for survival. Respondents also reported that poverty is a major cause of their vulnerability to drought. An increase in population, limited livelihood opportunities, caste system, lack of interest from the government sector, unawareness shaped their vulnerability to drought and other social issues. Based on the findings of this study, it is recommended that the local authorities shall create awareness about drought hazards and improve the resilience of communities against drought. It is further suggested to develop, introduce and implement water harvesting practices at the community level to promote drought-resistant crops.

Keywords: migration, vulnerability, awareness, Drought

Procedia PDF Downloads 132
214 Investigation of Mass Transfer for RPB Distillation at High Pressure

Authors: Amiza Surmi, Azmi Shariff, Sow Mun Serene Lock

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In recent decades, there has been a significant emphasis on the pivotal role of Rotating Packed Beds (RPBs) in absorption processes, encompassing the removal of Volatile Organic Compounds (VOCs) from groundwater, deaeration, CO2 absorption, desulfurization, and similar critical applications. The primary focus is elevating mass transfer rates, enhancing separation efficiency, curbing power consumption, and mitigating pressure drops. Additionally, substantial efforts have been invested in exploring the adaptation of RPB technology for offshore deployment. This comprehensive study delves into the intricacies of nitrogen removal under low temperature and high-pressure conditions, employing the high gravity principle via innovative RPB distillation concept with a specific emphasis on optimizing mass transfer. Based on the author's knowledge and comprehensive research, no cryogenic experimental testing was conducted to remove nitrogen via RPB. The research identifies pivotal process control factors through meticulous experimental testing, with pressure, reflux ratio, and reboil ratio emerging as critical determinants in achieving the desired separation performance. The results are remarkable, with nitrogen removal reaching less than one mole% in the Liquefied Natural Gas (LNG) product and less than three moles% methane in the nitrogen-rich gas stream. The study further unveils the mass transfer coefficient, revealing a noteworthy trend of decreasing Number of Transfer Units (NTU) and Area of Transfer Units (ATU) as the rotational speed escalates. Notably, the condenser and reboiler impose varying demands based on the operating pressure, with lower pressures at 12 bar requiring a more substantial duty than the 15-bar operation of the RPB. In pursuit of optimal energy efficiency, a meticulous sensitivity analysis is conducted, pinpointing the ideal combination of pressure and rotating speed that minimizes overall energy consumption. These findings underscore the efficiency of the RPB distillation approach in effecting efficient separation, even when operating under the challenging conditions of low temperature and high pressure. This achievement is attributed to a rigorous process control framework that diligently manages the operational pressure and temperature profile of the RPB. Nonetheless, the study's conclusions point towards the need for further research to address potential scaling challenges and associated risks, paving the way for the industrial implementation of this transformative technology.

Keywords: mass transfer coefficient, nitrogen removal, liquefaction, rotating packed bed

Procedia PDF Downloads 53
213 Impact of Elevated Temperature on Spot Blotch Development in Wheat and Induction of Resistance by Plant Growth Promoting Rhizobacteria

Authors: Jayanwita Sarkar, Usha Chakraborty, Bishwanath Chakraborty

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Plants are constantly interacting with various abiotic and biotic stresses. In changing climate scenario plants are continuously modifying physiological processes to adapt to changing environmental conditions which profoundly affect plant-pathogen interactions. Spot blotch in wheat is a fast-rising disease in the warmer plains of South Asia where the rise in minimum average temperature over most of the year already affecting wheat production. Hence, the study was undertaken to explore the role of elevated temperature in spot blotch disease development and modulation of antioxidative responses by plant growth promoting rhizobacteria (PGPR) for biocontrol of spot blotch at high temperature. Elevated temperature significantly increases the susceptibility of wheat plants to spot blotch causing pathogen Bipolaris sorokiniana. Two PGPR Bacillus safensis (W10) and Ochrobactrum pseudogrignonense (IP8) isolated from wheat (Triticum aestivum L.) and blady grass (Imperata cylindrical L.) rhizophere respectively, showing in vitro antagonistic activity against Bipolaris sorokiniana were tested for growth promotion and induction of resistance against spot blotch in wheat. GC-MS analysis showed that Bacillus safensis (W10) and Ochrobactrum pseudogrignonense (IP8) produced antifungal and antimicrobial compounds in culture. Seed priming with these two bacteria significantly increase growth, modulate antioxidative signaling and induce resistance and eventually reduce disease incidence in wheat plants at optimum as well as elevated temperature which was further confirmed by indirect immunofluorescence assay using polyclonal antibody raised against Bipolaris sorokiniana. Application of the PGPR led to enhancement in activities of plant defense enzymes- phenylalanine ammonia lyase, peroxidase, chitinase and β-1,3 glucanase in infected leaves. Immunolocalization of chitinase and β-1,3 glucanase in PGPR primed and pathogen inoculated leaf tissue was further confirmed by transmission electron microscopy using PAb of chitinase, β-1,3 glucanase and gold labelled conjugates. Activity of ascorbate-glutathione redox cycle related enzymes such as ascorbate peroxidase, superoxide dismutase and glutathione reductase along with antioxidants such as carotenoids, glutathione and ascorbate and osmolytes like proline and glycine betain accumulation were also increased during disease development in PGPR primed plant in comparison to unprimed plants at high temperature. Real-time PCR analysis revealed enhanced expression of defense genes- chalcone synthase and phenyl alanineammonia lyase. Over expression of heat shock proteins like HSP 70, small HSP 26.3 and heat shock factor HsfA3 in PGPR primed plants effectively protect plants against spot blotch infection at elevated temperature as compared with control plants. Our results revealed dynamic biochemical cross talk between elevated temperature and spot blotch disease development and furthermore highlight PGPR mediated array of antioxidative and molecular alterations responsible for induction of resistance against spot blotch disease at elevated temperature which seems to be associated with up-regulation of defense genes, heat shock proteins and heat shock factors, less ROS production, membrane damage, increased expression of redox enzymes and accumulation of osmolytes and antioxidants.

Keywords: antioxidative enzymes, defense enzymes, elevated temperature, heat shock proteins, PGPR, Real-Time PCR, spot blotch, wheat

Procedia PDF Downloads 171
212 Oxalate Method for Assessing the Electrochemical Surface Area for Ni-Based Nanoelectrodes Used in Formaldehyde Sensing Applications

Authors: S. Trafela, X. Xua, K. Zuzek Rozmana

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In this study, we used an accurate and precise method to measure the electrochemically active surface areas (Aecsa) of nickel electrodes. Calculated Aecsa is really important for the evaluation of an electro-catalyst’s activity in electrochemical reaction of different organic compounds. The method involves the electrochemical formation of Ni(OH)₂ and NiOOH in the presence of adsorbed oxalate in alkaline media. The studies were carried out using cyclic voltammetry with polycrystalline nickel as a reference material and electrodeposited nickel nanowires, homogeneous and heterogeneous nickel films. From cyclic voltammograms, the charge (Q) values for the formation of Ni(OH)₂ and NiOOH surface oxides were calculated under various conditions. At sufficiently fast potential scan rates (200 mV s⁻¹), the adsorbed oxalate limits the growth of the surface hydroxides to a monolayer. Although the Ni(OH)₂/NiOOH oxidation peak overlaps with the oxygen evolution reaction, in the reverse scan, the NiOOH/ Ni(OH)₂ reduction peak is well-separated from other electrochemical processes and can be easily integrated. The values of these integrals were used to correlate experimentally measured charge density with an electrochemically active surface layer. The Aecsa of the nickel nanowires, homogeneous and heterogeneous nickel films were calculated to be Aecsa-NiNWs = 4.2066 ± 0.0472 cm², Aecsa-homNi = 1.7175 ± 0.0503 cm² and Aecsa-hetNi = 2.1862 ± 0.0154 cm². These valuable results were expanded and used in electrochemical studies of formaldehyde oxidation. As mentioned nickel nanowires, heterogeneous and homogeneous nickel films were used as simple and efficient sensor for formaldehyde detection. For this purpose, electrodeposited nickel electrodes were modified in 0.1 mol L⁻¹ solution of KOH in order to expect electrochemical activity towards formaldehyde. The investigation of the electrochemical behavior of formaldehyde oxidation in 0.1 mol L⁻¹ NaOH solution at the surface of modified nickel nanowires, homogeneous and heterogeneous nickel films were carried out by means of electrochemical techniques such as cyclic voltammetric and chronoamperometric methods. From investigations of effect of different formaldehyde concentrations (from 0.001 to 0.1 mol L⁻¹) on electrochemical signal - current we provided catalysis mechanism of formaldehyde oxidation, detection limit and sensitivity of nickel electrodes. The results indicated that nickel electrodes participate directly in the electrocatalytic oxidation of formaldehyde. In the overall reaction, formaldehyde in alkaline aqueous solution exists predominantly in form of CH₂(OH)O⁻, which is oxidized to CH₂(O)O⁻. Taking into account the determined (Aecsa) values we have been able to calculate the sensitivities: 7 mA mol L⁻¹ cm⁻² for nickel nanowires, 3.5 mA mol L⁻¹ cm⁻² for heterogeneous nickel film and 2 mA mol L⁻¹ cm⁻² for heterogeneous nickel film. The detection limit was 0.2 mM for nickel nanowires, 0.5 mM for porous Ni film and 0.8 mM for homogeneous Ni film. All of these results make nickel electrodes capable for further applications.

Keywords: electrochemically active surface areas, nickel electrodes, formaldehyde, electrocatalytic oxidation

Procedia PDF Downloads 161
211 Calibration of Residential Buildings Energy Simulations Using Real Data from an Extensive in situ Sensor Network – A Study of Energy Performance Gap

Authors: Mathieu Bourdeau, Philippe Basset, Julien Waeytens, Elyes Nefzaoui

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As residential buildings account for a third of the overall energy consumption and greenhouse gas emissions in Europe, building energy modeling is an essential tool to reach energy efficiency goals. In the energy modeling process, calibration is a mandatory step to obtain accurate and reliable energy simulations. Nevertheless, the comparison between simulation results and the actual building energy behavior often highlights a significant performance gap. The literature discusses different origins of energy performance gaps, from building design to building operation. Then, building operation description in energy models, especially energy usages and users’ behavior, plays an important role in the reliability of simulations but is also the most accessible target for post-occupancy energy management and optimization. Therefore, the present study aims to discuss results on the calibration ofresidential building energy models using real operation data. Data are collected through a sensor network of more than 180 sensors and advanced energy meters deployed in three collective residential buildings undergoing major retrofit actions. The sensor network is implemented at building scale and in an eight-apartment sample. Data are collected for over one year and half and coverbuilding energy behavior – thermal and electricity, indoor environment, inhabitants’ comfort, occupancy, occupants behavior and energy uses, and local weather. Building energy simulations are performed using a physics-based building energy modeling software (Pleaides software), where the buildings’features are implemented according to the buildingsthermal regulation code compliance study and the retrofit project technical files. Sensitivity analyses are performed to highlight the most energy-driving building features regarding each end-use. These features are then compared with the collected post-occupancy data. Energy-driving features are progressively replaced with field data for a step-by-step calibration of the energy model. Results of this study provide an analysis of energy performance gap on an existing residential case study under deep retrofit actions. It highlights the impact of the different building features on the energy behavior and the performance gap in this context, such as temperature setpoints, indoor occupancy, the building envelopeproperties but also domestic hot water usage or heat gains from electric appliances. The benefits of inputting field data from an extensive instrumentation campaign instead of standardized scenarios are also described. Finally, the exhaustive instrumentation solution provides useful insights on the needs, advantages, and shortcomings of the implemented sensor network for its replicability on a larger scale and for different use cases.

Keywords: calibration, building energy modeling, performance gap, sensor network

Procedia PDF Downloads 159
210 Burkholderia Cepacia ST 767 Causing a Three Years Nosocomial Outbreak in a Hemodialysis Unit

Authors: Gousilin Leandra Rocha Da Silva, Stéfani T. A. Dantas, Bruna F. Rossi, Erika R. Bonsaglia, Ivana G. Castilho, Terue Sadatsune, Ary Fernandes Júnior, Vera l. M. Rall

Abstract:

Kidney failure causes decreased diuresis and accumulation of nitrogenous substances in the body. To increase patient survival, hemodialysis is used as a partial substitute for renal function. However, contamination of the water used in this treatment, causing bacteremia in patients, is a worldwide concern. The Burkholderia cepacia complex (Bcc), a group of bacteria with more than 20 species, is frequently isolated from hemodialysis water samples and comprises opportunistic bacteria, affecting immunosuppressed patients, due to its wide variety of virulence factors, in addition to innate resistance to several antimicrobial agents, contributing to the permanence in the hospital environment and to the pathogenesis in the host. The objective of the present work was to characterize molecularly and phenotypically Bcc isolates collected from the water and dialysate of the Hemodialysis Unit and from the blood of patients at a Public Hospital in Botucatu, São Paulo, Brazil, between 2019 and 2021. We used 33 Bcc isolates, previously obtained from blood cultures from patients with bacteremia undergoing hemodialysis treatment (2019-2021) and 24 isolates obtained from water and dialysate samples in a Hemodialysis Unit (same period). The recA gene was sequenced to identify the specific species among the Bcc group. All isolates were tested for the presence of some genes that encode virulence factors such as cblA, esmR, zmpA and zmpB. Considering the epidemiology of the outbreak, the Bcc isolates were molecularly characterized by Multi Locus Sequence Type (MLST) and by pulsed-field gel electrophoresis (PFGE). The verification and quantification of biofilm in a polystyrene microplate were performed by submitting the isolates to different incubation temperatures (20°C, average water temperature and 35°C, optimal temperature for group growth). The antibiogram was performed with disc diffusion tests on agar, using discs impregnated with cefepime (30µg), ceftazidime (30µg), ciprofloxacin (5µg), gentamicin (10µg), imipenem (10µg), amikacin 30µg), sulfametazol/trimethoprim (23.75/1.25µg) and ampicillin/sulbactam (10/10µg). The presence of ZmpB was identified in all isolates, while ZmpA was observed in 96.5% of the isolates, while none of them presented the cblA and esmR genes. The antibiogram of the 33 human isolates indicated that all were resistant to gentamicin, colistin, ampicillin/sulbactam and imipenem. 16 (48.5%) isolates were resistant to amikacin and lower rates of resistance were observed for meropenem, ceftazidime, cefepime, ciprofloxacin and piperacycline/tazobactam (6.1%). All isolates were sensitive to sulfametazol/trimethoprim, levofloxacin and tigecycline. As for the water isolates, resistance was observed only to gentamicin (34.8%) and imipenem (17.4%). According to PFGE results, all isolates obtained from humans and water belonged to the same pulsotype (1), which was identified by recA sequencing as B. cepacia¸, belonging to sequence type ST-767. By observing a single pulse type over three years, one can observe the persistence of this isolate in the pipeline, contaminating patients undergoing hemodialysis, despite the routine disinfection of water with peracetic acid. This persistence is probably due to the production of biofilm, which protects bacteria from disinfectants and, making this scenario more critical, several isolates proved to be multidrug-resistant (resistance to at least three groups of antimicrobials), turning the patient care even more difficult.

Keywords: hemodialysis, burkholderia cepacia, PFGE, MLST, multi drug resistance

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209 Development of Anti-Fouling Surface Features Bioinspired by the Patterned Micro-Textures of the Scophthalmus rhombus (Brill)

Authors: Ivan Maguire, Alan Barrett, Alex Forte, Sandra Kwiatkowska, Rohit Mishra, Jens Ducrèe, Fiona Regan

Abstract:

Biofouling is defined as the gradual accumulation of Biomimetics refers to the use and imitation of principles copied from nature. Biomimetics has found interest across many commercial disciplines. Among many biological objects and their functions, aquatic animals deserve a special attention due to their antimicrobial capabilities resulting from chemical composition, surface topography or other behavioural defences, which can be used as an inspiration for antifouling technology. Marine biofouling has detrimental effects on seagoing vessels, both commercial and leisure, as well as on oceanographic sensors, offshore drilling rigs, and aquaculture installations. Sensor optics, membranes, housings and platforms can become fouled leading to problems with sensor performance and data integrity. While many anti-fouling solutions are currently being investigated as a cost-cutting measure, biofouling settlement may also be prevented by creating a surface that does not satisfy the settlement conditions. Brill (Scophthalmus rhombus) is a small flatfish occurring in marine waters of Mediterranean as well as Norway and Iceland. It inhabits sandy and muddy coastal waters from 5 to 80 meters. Its skin colour changes depending on environment, but generally is brownish with light and dark freckles, with creamy underside. Brill is oval in shape and its flesh is white. The aim of this study is to translate the unique micro-topography of the brill scale, to design marine inspired biomimetic surface coating and test it against a typical fouling organism. Following extensive study of scale topography of the brill fish (Scophthalmus rhombus) and the settlement behaviour of the diatom species Psammodictyon sp. via SEM, two state-of-the-art antifouling surface solutions were designed and investigated; A brill fish scale bioinspired surface pattern platform (BFD), and generic and uniformly-arrayed, circular micropillar platform (MPD), with offsets based on diatom species settlement behaviour. The BFD approach consists of different ~5 μm by ~90 μm Brill-replica patterns, grown to a 5 μm height, in a linear array pattern. The MPD approach utilises hexagonal-packed cylindrical pillars 10.6 μm in diameter, grown to a height of 5 μm, with vertical offset of 15 μm and horizontal offset of 26.6 μm. Photolithography was employed for microstructure growth, with a polydimethylsiloxane (PDMS) chip-based used as a testbed for diatom adhesion on both platforms. Settlement and adhesion tests were performed using this PDMS microfluidic chip through subjugation to centrifugal force via an in-house developed ‘spin-stand’ which features a motor, in combination with a high-resolution camera, for real-time observing diatom release from PDMS material. Diatom adhesion strength can therefore be determined based on the centrifugal force generated at varying rotational speeds. It is hoped that both the replica and bio-inspired solutions will give comparable anti-fouling results to these synthetic surfaces, whilst also assisting in determining whether anti-fouling solutions should predominantly be investigating either fully bioreplica-based, or a bioinspired, synthetically-based design.

Keywords: anti-fouling applications, bio-inspired microstructures, centrifugal microfluidics, surface modification

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208 Comparison of the Effectiveness of Tree Algorithms in Classification of Spongy Tissue Texture

Authors: Roza Dzierzak, Waldemar Wojcik, Piotr Kacejko

Abstract:

Analysis of the texture of medical images consists of determining the parameters and characteristics of the examined tissue. The main goal is to assign the analyzed area to one of two basic groups: as a healthy tissue or a tissue with pathological changes. The CT images of the thoracic lumbar spine from 15 healthy patients and 15 with confirmed osteoporosis were used for the analysis. As a result, 120 samples with dimensions of 50x50 pixels were obtained. The set of features has been obtained based on the histogram, gradient, run-length matrix, co-occurrence matrix, autoregressive model, and Haar wavelet. As a result of the image analysis, 290 descriptors of textural features were obtained. The dimension of the space of features was reduced by the use of three selection methods: Fisher coefficient (FC), mutual information (MI), minimization of the classification error probability and average correlation coefficients between the chosen features minimization of classification error probability (POE) and average correlation coefficients (ACC). Each of them returned ten features occupying the initial place in the ranking devised according to its own coefficient. As a result of the Fisher coefficient and mutual information selections, the same features arranged in a different order were obtained. In both rankings, the 50% percentile (Perc.50%) was found in the first place. The next selected features come from the co-occurrence matrix. The sets of features selected in the selection process were evaluated using six classification tree methods. These were: decision stump (DS), Hoeffding tree (HT), logistic model trees (LMT), random forest (RF), random tree (RT) and reduced error pruning tree (REPT). In order to assess the accuracy of classifiers, the following parameters were used: overall classification accuracy (ACC), true positive rate (TPR, classification sensitivity), true negative rate (TNR, classification specificity), positive predictive value (PPV) and negative predictive value (NPV). Taking into account the classification results, it should be stated that the best results were obtained for the Hoeffding tree and logistic model trees classifiers, using the set of features selected by the POE + ACC method. In the case of the Hoeffding tree classifier, the highest values of three parameters were obtained: ACC = 90%, TPR = 93.3% and PPV = 93.3%. Additionally, the values of the other two parameters, i.e., TNR = 86.7% and NPV = 86.6% were close to the maximum values obtained for the LMT classifier. In the case of logistic model trees classifier, the same ACC value was obtained ACC=90% and the highest values for TNR=88.3% and NPV= 88.3%. The values of the other two parameters remained at a level close to the highest TPR = 91.7% and PPV = 91.6%. The results obtained in the experiment show that the use of classification trees is an effective method of classification of texture features. This allows identifying the conditions of the spongy tissue for healthy cases and those with the porosis.

Keywords: classification, feature selection, texture analysis, tree algorithms

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207 Using Fractal Architectures for Enhancing the Thermal-Fluid Transport

Authors: Surupa Shaw, Debjyoti Banerjee

Abstract:

Enhancing heat transfer in compact volumes is a challenge when constrained by cost issues, especially those associated with requirements for minimizing pumping power consumption. This is particularly acute for electronic chip cooling applications. Technological advancements in microelectronics have led to development of chip architectures that involve increased power consumption. As a consequence packaging, technologies are saddled with needs for higher rates of power dissipation in smaller form factors. The increasing circuit density, higher heat flux values for dissipation and the significant decrease in the size of the electronic devices are posing thermal management challenges that need to be addressed with a better design of the cooling system. Maximizing surface area for heat exchanging surfaces (e.g., extended surfaces or “fins”) can enable dissipation of higher levels of heat flux. Fractal structures have been shown to maximize surface area in compact volumes. Self-replicating structures at multiple length scales are called “Fractals” (i.e., objects with fractional dimensions; unlike regular geometric objects, such as spheres or cubes whose volumes and surface area values scale as integer values of the length scale dimensions). Fractal structures are expected to provide an appropriate technology solution to meet these challenges for enhanced heat transfer in the microelectronic devices by maximizing surface area available for heat exchanging fluids within compact volumes. In this study, the effect of different fractal micro-channel architectures and flow structures on the enhancement of transport phenomena in heat exchangers is explored by parametric variation of fractal dimension. This study proposes a model that would enable cost-effective solutions for thermal-fluid transport for energy applications. The objective of this study is to ascertain the sensitivity of various parameters (such as heat flux and pressure gradient as well as pumping power) to variation in fractal dimension. The role of the fractal parameters will be instrumental in establishing the most effective design for the optimum cooling of microelectronic devices. This can help establish the requirement of minimal pumping power for enhancement of heat transfer during cooling. Results obtained in this study show that the proposed models for fractal architectures of microchannels significantly enhanced heat transfer due to augmentation of surface area in the branching networks of varying length-scales.

Keywords: fractals, microelectronics, constructal theory, heat transfer enhancement, pumping power enhancement

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206 Novel EGFR Ectodomain Mutations and Resistance to Anti-EGFR and Radiation Therapy in H&N Cancer

Authors: Markus Bredel, Sindhu Nair, Hoa Q. Trummell, Rajani Rajbhandari, Christopher D. Willey, Lewis Z. Shi, Zhuo Zhang, William J. Placzek, James A. Bonner

Abstract:

Purpose: EGFR-targeted monoclonal antibodies (mAbs) provide clinical benefit in some patients with H&N squamous cell carcinoma (HNSCC), but others progress with minimal response. Missense mutations in the EGFR ectodomain (ECD) can be acquired under mAb therapy by mimicking the effect of large deletions on receptor untethering and activation. Little is known about the contribution of EGFR ECD mutations to EGFR activation and anti-EGFR response in HNSCC. Methods: We selected patient-derived HNSCC cells (UM-SCC-1) for resistance to mAb Cetuximab (CTX) by repeated, stepwise exposure to mimic what may occur clinically and identified two concurrent EGFR ECD mutations (UM-SCC-1R). We examined the competence of the mutants to bind EGF ligand or CTX. We assessed the potential impact of the mutations through visual analysis of space-filling models of the native sidechains in the original structures vs. their respective side-chain mutations. We performed CRISPR in combination with site-directed mutagenesis to test for the effect of the mutants on ligand-independent EGFR activation and sorting. We determined the effects on receptor internalization, endocytosis, downstream signaling, and radiation sensitivity. Results: UM-SCC-1R cells carried two non-synonymous missense mutations (G33S and N56K) mapping to domain I in or near the EGF binding pocket of the EGFR ECD. Structural modeling predicted that these mutants restrict the adoption of a tethered, inactive EGFR conformation while not permitting association of EGFR with the EGF ligand or CTX. Binding studies confirmed that the mutant, untethered receptor displayed a reduced affinity for both EGF and CTX but demonstrated sustained activation and presence at the cell surface with diminished internalization and sorting for endosomal degradation. Single and double-mutant models demonstrated that the G33S mutant is dominant over the N56K mutant in its effect on EGFR activation and EGF binding. CTX-resistant UM-SCC-1R cells demonstrated cross-resistance to mAb Panitumuab but, paradoxically, remained sensitive to the reversible receptor tyrosine kinase inhibitor Erlotinib. Conclusions: HNSCC cells can select for EGFR ECD mutations under EGFR mAb exposure that converge to trap the receptor in an open, constitutively activated state. These mutants impede the receptor’s competence to bind mAbs and EGF ligand and alter its endosomal trafficking, possibly explaining certain cases of clinical mAb and radiation resistance.

Keywords: head and neck cancer, EGFR mutation, resistance, cetuximab

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