Search results for: surrogate
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 104

Search results for: surrogate

44 Development of Innovative Nuclear Fuel Pellets Using Additive Manufacturing

Authors: Paul Lemarignier, Olivier Fiquet, Vincent Pateloup

Abstract:

In line with the strong desire of nuclear energy players to have ever more effective products in terms of safety, research programs on E-ATF (Enhanced-Accident Tolerant Fuels) that are more resilient, particularly to the loss of coolant, have been launched in all countries with nuclear power plants. Among the multitude of solutions being developed internationally, carcinoembryonic antigen (CEA) and its partners are investigating a promising solution, which is the realization of CERMET (CERamic-METal) type fuel pellets made of a matrix of fissile material, uranium dioxide UO2, which has a low thermal conductivity, and a metallic phase with a high thermal conductivity to improve heat evacuation. Work has focused on the development by powder metallurgy of micro-structured CERMETs, characterized by networks of metallic phase embedded in the UO₂ matrix. Other types of macro-structured CERMETs, based on concepts proposed by thermal simulation studies, have been developed with a metallic phase with a specific geometry to optimize heat evacuation. This solution could not be developed using traditional processes, so additive manufacturing, which revolutionizes traditional design principles, is used to produce these innovative prototype concepts. At CEA Cadarache, work is first carried out on a non-radioactive surrogate material, alumina, in order to acquire skills and to develop the equipment, in particular the robocasting machine, an additive manufacturing technique selected for its simplicity and the possibility of optimizing the paste formulations. A manufacturing chain was set up, with the pastes production, the 3D printing of pellets, and the associated thermal post-treatment. The work leading to the first elaborations of macro-structured alumina/molybdenum CERMETs will be presented. This work was carried out with the support of Framatome and EdF.

Keywords: additive manufacturing, alumina, CERMET, molybdenum, nuclear safety

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43 A Hierarchical Bayesian Calibration of Data-Driven Models for Composite Laminate Consolidation

Authors: Nikolaos Papadimas, Joanna Bennett, Amir Sakhaei, Timothy Dodwell

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Composite modeling of consolidation processes is playing an important role in the process and part design by indicating the formation of possible unwanted prior to expensive experimental iterative trial and development programs. Composite materials in their uncured state display complex constitutive behavior, which has received much academic interest, and this with different models proposed. Errors from modeling and statistical which arise from this fitting will propagate through any simulation in which the material model is used. A general hyperelastic polynomial representation was proposed, which can be readily implemented in various nonlinear finite element packages. In our case, FEniCS was chosen. The coefficients are assumed uncertain, and therefore the distribution of parameters learned using Markov Chain Monte Carlo (MCMC) methods. In engineering, the approach often followed is to select a single set of model parameters, which on average, best fits a set of experiments. There are good statistical reasons why this is not a rigorous approach to take. To overcome these challenges, A hierarchical Bayesian framework was proposed in which population distribution of model parameters is inferred from an ensemble of experiments tests. The resulting sampled distribution of hyperparameters is approximated using Maximum Entropy methods so that the distribution of samples can be readily sampled when embedded within a stochastic finite element simulation. The methodology is validated and demonstrated on a set of consolidation experiments of AS4/8852 with various stacking sequences. The resulting distributions are then applied to stochastic finite element simulations of the consolidation of curved parts, leading to a distribution of possible model outputs. With this, the paper, as far as the authors are aware, represents the first stochastic finite element implementation in composite process modelling.

Keywords: data-driven , material consolidation, stochastic finite elements, surrogate models

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42 A Neural Network for the Prediction of Contraction after Burn Injuries

Authors: Ginger Egberts, Marianne Schaaphok, Fred Vermolen, Paul van Zuijlen

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A few years ago, a promising morphoelastic model was developed for the simulation of contraction formation after burn injuries. Contraction can lead to a serious reduction in physical mobility, like a reduction in the range-of-motion of joints. If this is the case in a healing burn wound, then this is referred to as a contracture that needs medical intervention. The morphoelastic model consists of a set of partial differential equations describing both a chemical part and a mechanical part in dermal wound healing. These equations are solved with the numerical finite element method (FEM). In this method, many calculations are required on each of the chosen elements. In general, the more elements, the more accurate the solution. However, the number of elements increases rapidly if simulations are performed in 2D and 3D. In that case, it not only takes longer before a prediction is available, the computation also becomes more expensive. It is therefore important to investigate alternative possibilities to generate the same results, based on the input parameters only. In this study, a surrogate neural network has been designed to mimic the results of the one-dimensional morphoelastic model. The neural network generates predictions quickly, is easy to implement, and there is freedom in the choice of input and output. Because a neural network requires extensive training and a data set, it is ideal that the one-dimensional FEM code generates output quickly. These feed-forward-type neural network results are very promising. Not only can the network give faster predictions, but it also has a performance of over 99%. It reports on the relative surface area of the wound/scar, the total strain energy density, and the evolutions of the densities of the chemicals and mechanics. It is, therefore, interesting to investigate the applicability of a neural network for the two- and three-dimensional morphoelastic model for contraction after burn injuries.

Keywords: biomechanics, burns, feasibility, feed-forward NN, morphoelasticity, neural network, relative surface area wound

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41 Implementing of Indoor Air Quality Index in Hong Kong

Authors: Kwok W. Mui, Ling T. Wong, Tsz W. Tsang

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Many Hong Kong people nowadays spend most of their lifetime working indoor. Since poor Indoor Air Quality (IAQ) potentially leads to discomfort, ill health, low productivity and even absenteeism in workplaces, a call for establishing statutory IAQ control to safeguard the well-being of residents is urgently required. Although policies, strategies, and guidelines for workplace IAQ diagnosis have been developed elsewhere and followed with remedial works, some of those workplaces or buildings have relatively late stage of the IAQ problems when the investigation or remedial work started. Screening for IAQ problems should be initiated as it will provide information as a minimum provision of IAQ baseline requisite to the resolution of the problems. It is not practical to sample all air pollutants that exit. Nevertheless, as a statutory control, reliable, rapid screening is essential in accordance with a compromise strategy, which balances costs against detection of key pollutants. This study investigates the feasibility of using an IAQ index as a parameter of IAQ control in Hong Kong. The index is a screening parameter to identify the unsatisfactory workplace IAQ and will highlight where a fully effective IAQ monitoring and assessment is needed for an intensive diagnosis. There already exist a number of representative common indoor pollutants based on some extensive IAQ assessments. The selection of pollutants is surrogate to IAQ control consists of dilution, mitigation, and emission control. The IAQ Index and assessment will look at high fractional quantities of these common measurement parameters. With the support of the existing comprehensive regional IAQ database and the IAQ Index by the research team as the pre-assessment probability, and the unsatisfactory IAQ prevalence as the post-assessment probability from this study, thresholds of maintaining the current measures and performing a further IAQ test or IAQ remedial measures will be proposed. With justified resources, the proposed IAQ Index and assessment protocol might be a useful tool for setting up a practical public IAQ surveillance programme and policy in Hong Kong.

Keywords: assessment, index, indoor air quality, surveillance programme

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40 Size Optimization of Microfluidic Polymerase Chain Reaction Devices Using COMSOL

Authors: Foteini Zagklavara, Peter Jimack, Nikil Kapur, Ozz Querin, Harvey Thompson

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The invention and development of the Polymerase Chain Reaction (PCR) technology have revolutionised molecular biology and molecular diagnostics. There is an urgent need to optimise their performance of those devices while reducing the total construction and operation costs. The present study proposes a CFD-enabled optimisation methodology for continuous flow (CF) PCR devices with serpentine-channel structure, which enables the trade-offs between competing objectives of DNA amplification efficiency and pressure drop to be explored. This is achieved by using a surrogate-enabled optimisation approach accounting for the geometrical features of a CF μPCR device by performing a series of simulations at a relatively small number of Design of Experiments (DoE) points, with the use of COMSOL Multiphysics 5.4. The values of the objectives are extracted from the CFD solutions, and response surfaces created using the polyharmonic splines and neural networks. After creating the respective response surfaces, genetic algorithm, and a multi-level coordinate search optimisation function are used to locate the optimum design parameters. Both optimisation methods produced similar results for both the neural network and the polyharmonic spline response surfaces. The results indicate that there is the possibility of improving the DNA efficiency by ∼2% in one PCR cycle when doubling the width of the microchannel to 400 μm while maintaining the height at the value of the original design (50μm). Moreover, the increase in the width of the serpentine microchannel is combined with a decrease in its total length in order to obtain the same residence times in all the simulations, resulting in a smaller total substrate volume (32.94% decrease). A multi-objective optimisation is also performed with the use of a Pareto Front plot. Such knowledge will enable designers to maximise the amount of DNA amplified or to minimise the time taken throughout thermal cycling in such devices.

Keywords: PCR, optimisation, microfluidics, COMSOL

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39 Competitive DNA Calibrators as Quality Reference Standards (QRS™) for Germline and Somatic Copy Number Variations/Variant Allelic Frequencies Analyses

Authors: Eirini Konstanta, Cedric Gouedard, Aggeliki Delimitsou, Stefania Patera, Samuel Murray

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Introduction: Quality reference DNA standards (QRS) for molecular testing by next-generation sequencing (NGS) are essential for accurate quantitation of copy number variations (CNV) for germline and variant allelic frequencies (VAF) for somatic analyses. Objectives: Presently, several molecular analytics for oncology patients are reliant upon quantitative metrics. Test validation and standardisation are also reliant upon the availability of surrogate control materials allowing for understanding test LOD (limit of detection), sensitivity, specificity. We have developed a dual calibration platform allowing for QRS pairs to be included in analysed DNA samples, allowing for accurate quantitation of CNV and VAF metrics within and between patient samples. Methods: QRS™ blocks up to 500nt were designed for common NGS panel targets incorporating ≥ 2 identification tags (IDTDNA.com). These were analysed upon spiking into gDNA, somatic, and ctDNA using a proprietary CalSuite™ platform adaptable to common LIMS. Results: We demonstrate QRS™ calibration reproducibility spiked to 5–25% at ± 2.5% in gDNA and ctDNA. Furthermore, we demonstrate CNV and VAF within and between samples (gDNA and ctDNA) with the same reproducibility (± 2.5%) in a clinical sample of lung cancer and HBOC (EGFR and BRCA1, respectively). CNV analytics was performed with similar accuracy using a single pair of QRS calibrators when using multiple single targeted sequencing controls. Conclusion: Dual paired QRS™ calibrators allow for accurate and reproducible quantitative analyses of CNV, VAF, intrinsic sample allele measurement, inter and intra-sample measure not only simplifying NGS analytics but allowing for monitoring clinically relevant biomarker VAF across patient ctDNA samples with improved accuracy.

Keywords: calibrator, CNV, gene copy number, VAF

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38 The Effects of Cardiovascular Risk on Age-Related Cognitive Decline in Healthy Older Adults

Authors: A. Badran, M. Hollocks, H. Markus

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Background: Common risk factors for cardiovascular disease are associated with age-related cognitive decline. There has been much interest in treating modifiable cardiovascular risk factors in the hope of reducing cognitive decline. However, there is currently no validated neuropsychological test to assess the subclinical cognitive effects of vascular risk. The Brief Memory and Executive Test (BMET) is a clinical screening tool, which was originally designed to be sensitive and specific to Vascular Cognitive Impairment (VCI), an impairment characterised by decline in frontally-mediated cognitive functions (e.g. Executive Function and Processing Speed). Objective: To cross-sectionally assess the validity of the BMET as a measure of the subclinical effects of vascular risk on cognition, in an otherwise healthy elderly cohort. Methods: Data from 346 participants (57 ± 10 years) without major neurological or psychiatric disorders were included in this study, gathered as part of a previous multicentre validation study for the BMET. Framingham Vascular Age was used as a surrogate measure of vascular risk, incorporating several established risk factors. Principal Components Analysis of the subtests was used to produce common constructs: an index for Memory and another for Executive Function/Processing Speed. Univariate General Linear models were used to relate Vascular Age to performance on Executive Function/Processing Speed and Memory subtests of the BMET, adjusting for Age, Premorbid Intelligence and Ethnicity. Results: Adverse vascular risk was associated with poorer performance on both the Memory and Executive Function/Processing Speed indices, adjusted for Age, Premorbid Intelligence and Ethnicity (p=0.011 and p<0.001, respectively). Conclusions: Performance on the BMET reflects the subclinical effects of vascular risk on cognition, in age-related cognitive decline. Vascular risk is associated with decline in both Executive Function/Processing Speed and Memory groups of subtests. Future studies are needed to explore whether treating vascular risk factors can effectively reduce age-related cognitive decline.

Keywords: age-related cognitive decline, vascular cognitive impairment, subclinical cerebrovascular disease, cognitive aging

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37 An Ethnographic Study of Commercial Surrogacy Industry in India

Authors: Dalia Bhattacharjee

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Motherhood as an institution is considered as sacred. Reproduction and motherhood have always been a concern of the private space of home. However, with the emergence of technologies like the Assisted Reproductive Technologies (ARTs), this intimate area has moved into the public. A woman can now become a mother with artificial insemination done by expert medical professionals in a hospital. With this development, the meanings of motherhood and childrearing have altered. Mothers have been divided into ‘ovarian mothers’ (those who provide the eggs), ‘uterine mothers’ (those who carry out the pregnancy and give birth), and ‘social mothers’ (those who raise the child). Thus, the ART business deconstructs motherhood by defining who the biological mother is and who the social mother is and who – despite contributing parts or processes of her body to the life of the child is not a mother, but merely the donor of a product, be it the egg or the womb, which is owned by those who are favoured by the contract. The industry of commercial surrogacy in India has been estimated to be of $2.3 billion as of 2012. There are many women who work as surrogate mothers in this industry for the exchange of money. It runs like a full-fledged business guided by a highly profit oriented capitalist market. The reproductive labourers are identified as mere womb renters or victims and not as active agents in such arrangements. Such a discourse undercuts the agency exercised by the women. The present study is an ethnography into the commercial surrogacy industry in India. This journey furthers the understanding of the dilemmas faced by the reproductive labourers. The paper emphasizes on the experiences of reproduction and motherhood outside the private space of the home in the commercial surrogacy industry in India, and, argues that this multiplicity of experiences need much focus and attention, where, the consumer becomes ‘the’ citizen and the women workers continue to be victims. The study draws on the narratives of the reproductive labourers, who remain at the center, and yet, at the periphery of such arrangements. This feminist ethnography is informed by the feminist standpoint theory to account for and analyse these varied experiences which further the understanding of the dilemmas faced by the reproductive labourers.

Keywords: commercial surrogacy, ethnography, motherhood, standpoint theory

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36 EEG and ABER Abnormalities in Children with Speech and Language Delay

Authors: Bharati Mehta, Manish Parakh, Bharti Bhandari, Sneha Ambwani

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Speech and language delay (SLD) is seen commonly as a co-morbidity in children having severe resistant focal and generalized, syndromic and symptomatic epilepsies. It is however not clear whether epilepsy contributes to or is a mere association in the pathogenesis of SLD. Also, it is acknowledged that Auditory Brainstem Evoked Responses (ABER), besides used for evaluating hearing threshold, also aid in prognostication of neurological disorders and abnormalities in the hearing pathway in the brainstem. There is no circumscribed or surrogate neurophysiologic laboratory marker to adjudge the extent of SLD. The current study was designed to evaluate the abnormalities in Electroencephalography (EEG) and ABER in children with SLD who do not have an overt hearing deficit or autism. 94 children of age group 2-8 years with predominant SLD and without any gross motor developmental delay, head injury, gross hearing disorder, cleft lip/palate and autism were selected. Standard video Electroencephalography using the 10:20 international system and ABER after click stimulus with intensities 110 db until 40 db was performed in all children. EEG was abnormal in 47.9% (n= 45; 36 boys and 9 girls) children. In the children with abnormal EEG, 64.5% (n=29) had an abnormal background, 57.8% (n=27) had presence of generalized interictal epileptiform discharges (IEDs), 20% (n=9) had focal epileptiform discharges exclusively from left side and 33.3% (n=15) had multifocal IEDs occurring both in isolation or associated with generalised abnormalities. In ABER, surprisingly, the peak latencies for waves I, III & V, inter-peak latencies I-III & I-V, III-V and wave amplitude ratio V/I, were found within normal limits in both ears of all the children. Thus in the current study it is certain that presence of generalized IEDs in EEG are seen in higher frequency with SLD and focal IEDs are seen exclusively in left hemisphere in these children. It may be possible that even with generalized EEG abnormalities present in these children, left hemispheric abnormalities as a part of this generalized dysfunction may be responsible for the speech and language dysfunction. The current study also emphasizes that ABER may not be routinely recommended as diagnostic or prognostic tool in children with SLD without frank hearing deficit or autism, thus reducing the burden on electro physiologists, laboratories and saving time and financial resources.

Keywords: ABER, EEG, speech, language delay

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35 The Effects of Physiological Stress on Global and Regional Repolarisation in the Human Heart in Vivo

Authors: May Khei Hu, Kevin Leong, Fu Siong Ng, Nicholas Peter

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Introduction: Sympathetic stimulation has been recognised as a potent stimulus of arrhythmogenesis in various cardiac pathologies, possibly by augmenting dispersion of repolarisation. The effects of sympathetic stimulation in healthy subjects however remain unclear. It is, therefore, crucial to first establish the effects of physiological stress on dispersion of repolarisation in healthy subjects before understanding these effects in pathological cardiac conditions. We hypothesised that activation-recovery interval (ARI; which is a surrogate of action potential duration) and dispersion of repolarisation decrease on sympathetic stimulation. Methods: Eight patients aged 18-55 years with structurally normal hearts underwent head-up tilt test (HUTT) and exercise tolerance test (ETT) while wearing the electrocardiographic imaging (ECGi) vest. Patients later underwent CT scan and the epicardial potentials are reconstructed using the ECGi software. Activation and recovery times were determined from the acquired electrograms. ARI was calculated and later corrected using Bazett’s formula. Global and regional dispersion of repolarisation were determined from standard deviation of the corrected ARI (ARIc). One-way analysis of variance (ANOVA) and Wilcoxon test were used to evaluate statistical significance. Results: Global ARIc increased significantly [p<0.01] when patients were tilted upwards but decreased significantly after five minutes [p<0.01]. A subsequent post- hoc analysis revealed that the decrease in R-R was more substantial compared to the change in ARI, resulting in the observed increase in ARIc. Global ARIc decreased on peak exercise [p<0.01] but increased on recovery [p<0.01]. Global dispersion increased significantly on peak exercise [p<0.05] although there were no significant changes in regional dispersion. There were no significant changes in both global and regional dispersion during tilt. Conclusion: ARIc decreases upon sympathetic stimulation in healthy subjects. Global dispersion of repolarisation increases upon exercise although there were no changes in global or regional dispersion during orthostatic stress.

Keywords: dispersion of repolarisation, sympathetic stimulation, Head-up tilt test (HUTT), Exercise tolerance test (ETT), Electrocardiographic imaging (ECGi)

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34 Functional Characterization of Rv1019, a Putative TetR Family Transcriptional Regulator of Mycobacterium Tuberculosis H37Rv

Authors: Akhil Raj Pushparajan, Ranjit Ramachandran, Jijimole Gopi Reji, Ajay Kumar Ramakrishnan

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Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is one of the leading causes of death by an infectious disease. In spite of the availability of effective drugs and a vaccine, TB is a major health concern and was declared a global emergency by the World Health Organization (WHO). The success of intracellular pathogens like Mtb depends on its ability to overcome the challenging environment in the host. Gene regulation controlled by transcriptional regulators (TRs) plays a crucial role for the bacteria to adapt to the host environment. In vitro studies on gene regulatory mechanisms during dormancy and reactivation have provided insights into the adaptations employed by Mtb to survive in the host. Here we present our efforts to functionally characterize Rv1019, a putative TR of Mtb H37Rv which was found to be present at significantly varying levels during dormancy and reactivation in vitro. The expression of this protein in the dormancy-reactivation model was validated by qRT-PCR and western blot. By DNA- protein interaction studies and reporter assays we found that under normal laboratory conditions of growth this protein behaves as an auto-repressor and tetracycline was found to abrogate this repression by interfering with its ability to bind DNA. Further, by cDNA analysis, we found that this TR is co-transcribed with its downstream genes Rv1020 (mfd) and Rv1021 (mazG) which are involved in DNA damage response in Mtb. Constitutive expression of this regulator in the surrogate host M. smegmatis showed downregulation of the orthologues of downstream genes suggested that Rv1019 could negatively regulate these genes. Our finds also show that M. smegmatis expressing Rv1019 is sensitive to DNA damage suggests the role of this protein in regulating DNA damage response induced by oxidative stress. Because of its role in regulating DNA damage response which may help in the persistence of Mtb, Rv1019 could be used as a prospective target for therapeutic intervention to fight TB.

Keywords: auto-repressor, DNA repair, mycobacterium smegmatis, mycobacterium tuberculosis, tuberculosis

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33 Organ Dose Calculator for Fetus Undergoing Computed Tomography

Authors: Choonsik Lee, Les Folio

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Pregnant patients may undergo CT in emergencies unrelated with pregnancy, and potential risk to the developing fetus is of concern. It is critical to accurately estimate fetal organ doses in CT scans. We developed a fetal organ dose calculation tool using pregnancy-specific computational phantoms combined with Monte Carlo radiation transport techniques. We adopted a series of pregnancy computational phantoms developed at the University of Florida at the gestational ages of 8, 10, 15, 20, 25, 30, 35, and 38 weeks (Maynard et al. 2011). More than 30 organs and tissues and 20 skeletal sites are defined in each fetus model. We calculated fetal organ dose-normalized by CTDIvol to derive organ dose conversion coefficients (mGy/mGy) for the eight fetuses for consequential slice locations ranging from the top to the bottom of the pregnancy phantoms with 1 cm slice thickness. Organ dose from helical scans was approximated by the summation of doses from multiple axial slices included in the given scan range of interest. We then compared dose conversion coefficients for major fetal organs in the abdominal-pelvis CT scan of pregnancy phantoms with the uterine dose of a non-pregnant adult female computational phantom. A comprehensive library of organ conversion coefficients was established for the eight developing fetuses undergoing CT. They were implemented into an in-house graphical user interface-based computer program for convenient estimation of fetal organ doses by inputting CT technical parameters as well as the age of the fetus. We found that the esophagus received the least dose, whereas the kidneys received the greatest dose in all fetuses in AP scans of the pregnancy phantoms. We also found that when the uterine dose of a non-pregnant adult female phantom is used as a surrogate for fetal organ doses, root-mean-square-error ranged from 0.08 mGy (8 weeks) to 0.38 mGy (38 weeks). The uterine dose was up to 1.7-fold greater than the esophagus dose of the 38-week fetus model. The calculation tool should be useful in cases requiring fetal organ dose in emergency CT scans as well as patient dose monitoring.

Keywords: computed tomography, fetal dose, pregnant women, radiation dose

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32 Adolescent-Parent Relationship as the Most Important Factor in Preventing Mood Disorders in Adolescents: An Application of Artificial Intelligence to Social Studies

Authors: Elżbieta Turska

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Introduction: One of the most difficult times in a person’s life is adolescence. The experiences in this period may shape the future life of this person to a large extent. This is the reason why many young people experience sadness, dejection, hopelessness, sense of worthlessness, as well as losing interest in various activities and social relationships, all of which are often classified as mood disorders. As many as 15-40% adolescents experience depressed moods and for most of them they resolve and are not carried into adulthood. However, (5-6%) of those affected by mood disorders develop the depressive syndrome and as many as (1-3%) develop full-blown clinical depression. Materials: A large questionnaire was given to 2508 students, aged 13–16 years old, and one of its parts was the Burns checklist, i.e. the standard test for identifying depressed mood. The questionnaire asked about many aspects of the student’s life, it included a total of 53 questions, most of which had subquestions. It is important to note that the data suffered from many problems, the most important of which were missing data and collinearity. Aim: In order to identify the correlates of mood disorders we built predictive models which were then trained and validated. Our aim was not to be able to predict which students suffer from mood disorders but rather to explore the factors influencing mood disorders. Methods: The problems with data described above practically excluded using all classical statistical methods. For this reason, we attempted to use the following Artificial Intelligence (AI) methods: classification trees with surrogate variables, random forests and xgboost. All analyses were carried out with the use of the mlr package for the R programming language. Resuts: The predictive model built by classification trees algorithm outperformed the other algorithms by a large margin. As a result, we were able to rank the variables (questions and subquestions from the questionnaire) from the most to least influential as far as protection against mood disorder is concerned. Thirteen out of twenty most important variables reflect the relationships with parents. This seems to be a really significant result both from the cognitive point of view and also from the practical point of view, i.e. as far as interventions to correct mood disorders are concerned.

Keywords: mood disorders, adolescents, family, artificial intelligence

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31 Application and Utility of the Rale Score for Assessment of Clinical Severity in Covid-19 Patients

Authors: Naridchaya Aberdour, Joanna Kao, Anne Miller, Timothy Shore, Richard Maher, Zhixin Liu

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Background: COVID-19 has and continues to be a strain on healthcare globally, with the number of patients requiring hospitalization exceeding the level of medical support available in many countries. As chest x-rays are the primary respiratory radiological investigation, the Radiological Assessment of Lung Edema (RALE) score was used to quantify the extent of pulmonary infection on baseline imaging. Assessment of RALE score's reproducibility and associations with clinical outcome parameters were then evaluated to determine implications for patient management and prognosis. Methods: A retrospective study was performed with the inclusion of patients testing positive for COVID-19 on nasopharyngeal swab within a single Local Health District in Sydney, Australia and baseline x-ray imaging acquired between January to June 2020. Two independent Radiologists viewed the studies and calculated the RALE scores. Clinical outcome parameters were collected and statistical analysis was performed to assess RALE score reproducibility and possible associations with clinical outcomes. Results: A total of 78 patients met inclusion criteria with the age range of 4 to 91 years old. RALE score concordance between the two independent Radiologists was excellent (interclass correlation coefficient = 0.93, 95% CI = 0.88-0.95, p<0.005). Binomial logistics regression identified a positive correlation with hospital admission (1.87 OR, 95% CI= 1.3-2.6, p<0.005), oxygen requirement (1.48 OR, 95% CI= 1.2-1.8, p<0.005) and invasive ventilation (1.2 OR, 95% CI= 1.0-1.3, p<0.005) for each 1-point increase in RALE score. For each one year increased in age, there was a negative correlation with recovery (0.05 OR, 95% CI= 0.92-1.0, p<0.01). RALE scores above three were positively associated with hospitalization (Youden Index 0.61, sensitivity 0.73, specificity 0.89) and above six were positively associated with ICU admission (Youden Index 0.67, sensitivity 0.91, specificity 0.78). Conclusion: The RALE score can be used as a surrogate to quantify the extent of COVID-19 infection and has an excellent inter-observer agreement. The RALE score could be used to prognosticate and identify patients at high risk of deterioration. Threshold values may also be applied to predict the likelihood of hospital and ICU admission.

Keywords: chest radiography, coronavirus, COVID-19, RALE score

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30 Corneal Confocal Microscopy As a Surrogate Marker of Neuronal Pathology In Schizophrenia

Authors: Peter W. Woodruff, Georgios Ponirakis, Reem Ibrahim, Amani Ahmed, Hoda Gad, Ioannis N. Petropoulos, Adnan Khan, Ahmed Elsotouhy, Surjith Vattoth, Mahmoud K. M. Alshawwaf, Mohamed Adil Shah Khoodoruth, Marwan Ramadan, Anjushri Bhagat, James Currie, Ziyad Mahfoud, Hanadi Al Hamad, Ahmed Own, Peter Haddad, Majid Alabdulla, Rayaz A. Malik

Abstract:

Introduction:- We aimed to test the hypothesis that, using corneal confocal microscopy (a non-invasive method for assessing corneal nerve fibre integrity), patients with schizophrenia would show neuronal abnormalities compared with healthy participants. Schizophrenia is a neurodevelopmental and progressive neurodegenerative disease, for which there are no validated biomarkers. Corneal confocal microscopy (CCM) is a non-invasive ophthalmic imaging biomarker that can be used to detect neuronal abnormalities in neuropsychiatric syndromes. Methods:- Patients with schizophrenia (DSM-V criteria) without other causes of peripheral neuropathy and healthy controls underwent CCM, vibration perception threshold (VPT) and sudomotor function testing. The diagnostic accuracy of CCM in distinguishing patients from controls was assessed using the area under the curve (AUC) of the Receiver Operating Characterstics (ROC) curve. Findings:- Participants with schizophrenia (n=17) and controls (n=38) with comparable age (35.7±8.5 vs 35.6±12.2, P=0.96) were recruited. Patients with schizophrenia had significantly higher body weight (93.9±25.5 vs 77.1±10.1, P=0.02), lower Low Density Lipoproteins (2.6±1.0 vs 3.4±0.7, P=0.02), but comparable systolic and diastolic blood pressure, HbA1c, total cholesterol, triglycerides and High Density Lipoproteins were comparable with control participants. Patients with schizophrenia had significantly lower corneal nerve fiber density (CNFD, fibers/mm2) (23.5±7.8 vs 35.6±6.5, p<0.0001), branch density (CNBD, branches/mm2) (34.4±26.9 vs 98.1±30.6, p<0.0001), and fiber length (CNFL, mm/mm2) (14.3±4.7 vs 24.2±3.9, p<0.0001) but no difference in VPT (6.1±3.1 vs 4.5±2.8, p=0.12) and electrochemical skin conductance (61.0±24.0 vs 68.9±12.3, p=0.23) compared with controls. The diagnostic accuracy of CNFD, CNBD and CNFL to distinguish patients with schizophrenia from healthy controls were, according to the AUC, (95% CI): 87.0% (76.8-98.2), 93.2% (84.2-102.3), 93.2% (84.4-102.1), respectively. Conclusion:- In conclusion, CCM can be used to help identify neuronal changes and has a high diagnostic accuracy to distinguish subjects with schizophrenia from healthy controls.

Keywords:

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29 Mechanical Behavior of Hybrid Hemp/Jute Fibers Reinforced Polymer Composites at Liquid Nitrogen Temperature

Authors: B. Vinod, L. Jsudev

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Natural fibers as reinforcement in polymer matrix material is gaining lot of attention in recent years, as they are light in weight, less in cost, and ecologically advanced surrogate material to glass and carbon fibers in composites. Natural fibers like jute, sisal, coir, hemp, banana etc. have attracted substantial importance as a potential structural material because of its attractive features along with its good mechanical properties. Cryogenic applications of natural fiber reinforced polymer composites like cryogenic wind tunnels, cryogenic transport vessels, support structures in space shuttles and rockets are gaining importance. In these unique cryogenic applications, the requirements of polymer composites are extremely severe and complicated. These materials need to possess good mechanical and physical properties at cryogenic temperatures such as liquid helium (4.2 K), liquid hydrogen (20 K), liquid nitrogen (77 K), and liquid oxygen (90 K) temperatures, etc., to meet the high requirements by the cryogenic engineering applications. The objective of this work is to investigate the mechanical behavior of hybrid hemp/jute fibers reinforced epoxy composite material at liquid nitrogen temperature. Hemp and Jute fibers are used as reinforcement material as they have high specific strength, stiffness and good adhering property and has the potential to replace the synthetic fibers. Hybrid hemp/jute fibers reinforced polymer composite is prepared by hand lay-up method and test specimens are cut according to ASTM standards. These test specimens are dipped in liquid nitrogen for different time durations. The tensile properties, flexural properties and impact strength of the specimen are tested immediately after the specimens are removed from liquid nitrogen container. The experimental results indicate that the cryogenic treatment of the polymer composite has a significant effect on the mechanical properties of this material. The tensile properties and flexural properties of the hybrid hemp/jute fibers epoxy composite at liquid nitrogen temperature is higher than at room temperature. The impact strength of the material decreased after subjecting it to liquid nitrogen temperature.

Keywords: liquid nitrogen temperature, polymer composite, tensile properties, flexural properties

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28 Elaboration of Ceramic Metal Accident Tolerant Fuels by Additive Manufacturing

Authors: O. Fiquet, P. Lemarignier

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Additive manufacturing may find numerous applications in the nuclear industry, for the same reason as for other industries, to enlarge design possibilities and performances and develop fabrication methods as a flexible route for future innovation. Additive Manufacturing applications in the design of structural metallic components for reactors are already developed at a high Technology Readiness Level (TRL). In the case of a Pressured Water Reactor using uranium oxide fuel pellets, which are ceramics, the transposition of already optimized Additive Manufacturing (AM) processes to UO₂ remains a challenge, and the progress remains slow because, to our best knowledge, only a few laboratories have the capability of developing processes applicable to UO₂. After the Fukushima accident, numerous research fields emerged with the study of ATF (Accident tolerant Fuel) fuel concepts, which aimed to improve fuel behaviour. One item concerns the increase of the pellet thermal performance by, for example, the addition of high thermal conductivity material into fissile UO₂. This additive phase may be metallic, and the end product will constitute a CERMET composite. Innovative designs of an internal metallic framework are proposed based on predictive calculations. However, because the well-known reference pellet manufacturing methods impose many limitations, manufacturing such a composite remains an arduous task. Therefore, the AM process appears as a means of broadening the design possibilities of CERMET manufacturing. If the external form remains a standard cylindrical fuel pellet, the internal metallic design remains to be optimized based on process capabilities. This project also considers the limitation to a maximum of 10% volume of metal, which is a constraint neutron physics considerations impose. The AM technique chosen for this development is robocasting because of its simplicity and low-cost equipment. It remains, however, a challenge to adapt a ceramic 3D printing process for the fabrication of UO₂ fuel. The investigation starts with surrogate material, and the optimization of slurry feedstock is based on alumina. The paper will present the first printing of Al2O3-Mo CERMET and the expected transition from ceramic-based alumina to UO₂ CERMET.

Keywords: nuclear, fuel, CERMET, robocasting

Procedia PDF Downloads 31
27 Associations between Surrogate Insulin Resistance Indices and the Risk of Metabolic Syndrome in Children

Authors: Mustafa M. Donma, Orkide Donma

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A well-defined insulin resistance (IR) is one of the requirements for the good understanding and evaluation of metabolic syndrome (MetS). However, underlying causes for the development of IR are not clear. Endothelial dysfunction also participates in the pathogenesis of this disease. IR indices are being determined in various obesity groups and also in diagnosing MetS. Components of MetS have been well established and used in adult studies. However, there are some ambiguities particularly in the field of pediatrics. The aims of this study were to compare the performance of fasting blood glucose (FBG), one of MetS components, with some other IR indices and check whether FBG may be replaced by some other parameter or ratio for a better evaluation of pediatric MetS. Five-hundred and forty-nine children were involved in the study. Five groups were constituted. Groups 109, 40, 100, 166, 110, 24 children were included in normal-body mass index (N-BMI), overweight (OW), obese (OB), morbid obese (MO), MetS with two components (MetS2) and MetS with three components (MetS3) groups, respectively. Age and sex-adjusted BMI percentiles tabulated by World Health Organization were used for the classification of obesity groups. MetS components were determined. Aside from one of the MetS components-FBG, eight measures of IR [homeostatic model assessment of IR (HOMA-IR), homeostatic model assessment of beta cell function (HOMA-%β), alanine transaminase-to-aspartate transaminase ratio (ALT/AST), alanine transaminase (ALT), insulin (INS), insulin-to-FBG ratio (INS/FBG), the product of fasting triglyceride and glucose (TyG) index, McAuley index] were evaluated. Statistical analyses were performed. A p value less than 0.05 was accepted as the statistically significance degree. Mean values for BMI of the groups were 15.7 kg/m2, 21.0 kg/m2, 24.7 kg/m2, 27.1 kg/m2, 28.7 kg/m2, 30.4 kg/m2 for N-BMI, OW, OB, MO, MetS2, MetS3, respectively. Differences between the groups were significant (p < 0.001). The only exception was MetS2-MetS3 couple, in spite of an increase detected in MetS3 group. Waist-to-hip circumference ratios significantly differed only for N-BMI vs, OB, MO, MetS2; OW vs MO; OB vs MO, MetS2 couples. ALT and ALT/AST did not differ significantly among MO-MetS2-MetS3. HOMA-%β differed only between MO and MetS2. INS/FBG, McAuley index and TyG were not significant between MetS2 and MetS3. HOMA-IR and FBG were not significant between MO and MetS2. INS was the only parameter, which showed statistically significant differences between MO-MetS2, MO-MetS3, and MetS2-MetS3. In conclusion, these findings have suggested that FBG presently considered as one of the five MetS components, may be replaced by INS during the evaluation of pediatric morbid obesity and MetS.

Keywords: children, insulin resistance indices, metabolic syndrome, obesity

Procedia PDF Downloads 98
26 Challenges and Practical Tips for Advance Care Planning and End-of-Life Communications With Cancer Patients in Global Pandemic

Authors: Poonam Goswami

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Background: The diagnosis of a serious illness like cancer can have an impact on a patient’s emotional well-being and may result in psychological symptoms, anxiety, depression, and loss of control. Advance care planning discussions ensure patients’ values and goals of care, including patients’ freedom to choose their place of death, are respected. Unfortunately, these discussions are often delayed and are not initiated early in patients’ cancer trajectory. As a result, patients’ wishes often remains unknown until the last phase of their life. Evidence suggests that many patients inappropriately receive aggressive treatment near the end of life, which does lead to higher resource utilization, decreased quality of life, and increased cost. Additionally, the novel coronavirus disease 2019 (COVID-19) pandemic challenged the health care systems worldwide and raised important ethical issues, especially regarding the potential need for rationing health care in the context of scarce resources and crisis capacity. The importance of goal concordant care is now even substantially important and is heightened in the context of this pandemic. Problem: Although there is growing evidence on the effects of the ACP on the completion of advanced directives, improved patient and family concordance for preferences for medical care, and receipt of care, there is still a lack of standardized ACP conversation strategies for patients with cancer. Methods: The Key concepts of ACP include (1) assessing patient and family readiness, (2) identifying a surrogate decision maker ( medical power of attorney), (3) exploring patient and family understanding of the disease and treatment options,(4) discussing the values and goals of care, and options for end-of-life care, (5) documenting patient preferences in the medical record, and (6) revisiting the discussions at every change in the treatment plan and /or change in clinical status, including at every hospitalization. Conclusion/Implication for practice: Advance Care Planning (ACP) and end-of-life (EOL) discussions are important for patients, families, and health care providers. Adopting the verbal and nonverbal communication strategies can help overcome the barriers to effective communication on these difficult discussions. ACP with goals of care discussions should not be delayed until the patient is hospitalized.

Keywords: advance care planning, end of life, cancer, global, pandemic

Procedia PDF Downloads 101
25 Material Response Characterisation of a PolyJet 3D Printed Human Infant Skull

Authors: G. A. Khalid, R. Prabhu, W. Whittington, M. D. Jones

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To establish a causal relationship of infant head injury consequences, this present study addresses the necessary challenges of cranial geometry and the physical response complexities of the paediatric head tissues. Herein, we describe a new approach to characterising and understanding infant head impact mechanics by developing printed head models, using high resolution clinical postmortem imaging, to provide the most complete anatomical representation currently available, and biological material response data-matched polypropylene polymers, to replicate the relative mechanical response properties of immature cranial bone, sutures and fontanelles. Additive manufacturing technology was applied to creating a physical polymeric model of a newborn infant skull, using PolyJet printed materials. Infant skull materials responses, were matched by a response characterisation study, utilising uniaxial tensile testing (1 mm min-1 loading rate), to determine: the stiffness, ultimate tensile strength and maximum strain of rigid and rubber additively manufactured acrylates. The results from the mechanical experiments confirm that the polymeric materials RGD835 Vero White Plus (White), representing the frontal and parietal bones; RGD8510- DM Rigid Light Grey25 (Grey), representing the occipital bone; and FLX9870-DM (Black) representing the suture and fontanelles, were found to show a close stiffness -correlation (E) at ambient temperatures. A 3D physical model of infant head was subsequently printed from the matched materials and subsequently validated against results obtained from a series of Post Mortem Human Surrogate (PMHS) tests. A close correlation was demonstrated between the model impact tests and the PMHS. This study, therefore, represents a key step towards applying printed physical models to understanding head injury biomechanics and is useful in the efforts to predict and mitigate head injury consequences in infants, whether accidental or by abuse.

Keywords: infant head trauma, infant skull, material response, post mortem human subjects, polyJet printing

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24 Novel Adomet Analogs as Tools for Nucleic Acids Labeling

Authors: Milda Nainyte, Viktoras Masevicius

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Biological methylation is a methyl group transfer from S-adenosyl-L-methionine (AdoMet) onto N-, C-, O- or S-nucleophiles in DNA, RNA, proteins or small biomolecules. The reaction is catalyzed by enzymes called AdoMet-dependent methyltransferases (MTases), which represent more than 3 % of the proteins in the cell. As a general mechanism, the methyl group from AdoMet replaces a hydrogen atom of nucleophilic center producing methylated DNA and S-adenosyl-L-homocysteine (AdoHcy). Recently, DNA methyltransferases have been used for the sequence-specific, covalent labeling of biopolymers. Two types of MTase catalyzed labeling of biopolymers are known, referred as two-step and one-step. During two-step labeling, an alkylating fragment is transferred onto DNA in a sequence-specific manner and then the reporter group, such as biotin, is attached for selective visualization using suitable chemistries of coupling. This approach of labeling is quite difficult and the chemical hitching does not always proceed at 100 %, but in the second step the variety of reporter groups can be selected and that gives the flexibility for this labeling method. In the one-step labeling, AdoMet analog is designed with the reporter group already attached to the functional group. Thus, the one-step labeling method would be more comfortable tool for labeling of biopolymers in order to prevent additional chemical reactions and selection of reaction conditions. Also, time costs would be reduced. However, effective AdoMet analog appropriate for one-step labeling of biopolymers and containing cleavable bond, required for reduction of PCR interferation, is still not known. To expand the practical utility of this important enzymatic reaction, cofactors with activated sulfonium-bound side-chains have been produced and can serve as surrogate cofactors for a variety of wild-type and mutant DNA and RNA MTases enabling covalent attachment of these chains to their target sites in DNA, RNA or proteins (the approach named methyltransferase-directed Transfer of Activated Groups, mTAG). Compounds containing hex-2-yn-1-yl moiety has proved to be efficient alkylating agents for labeling of DNA. Herein we describe synthetic procedures for the preparation of N-biotinoyl-N’-(pent-4-ynoyl)cystamine starting from the coupling of cystamine with pentynoic acid and finally attaching the biotin as a reporter group. The synthesis of the first AdoMet based cofactor containing a cleavable reporter group and appropriate for one-step labeling was developed.

Keywords: adoMet analogs, DNA alkylation, cofactor, methyltransferases

Procedia PDF Downloads 168
23 Tumour-Associated Tissue Eosinophilia as a Prognosticator in Oral Squamous Cell Carcinoma

Authors: Karen Boaz, C. R. Charan

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Background: The infiltration of tumour stroma by eosinophils, Tumor-Associated Tissue Eosinophilia (TATE), is known to modulate the progression of Oral Squamous Cell Carcinoma (OSCC). Eosinophils have direct tumoricidal activity by release of cytotoxic proteins and indirectly they enhance permeability into tumor cells enabling penetration of tumoricidal cytokines. Also, eosinophils may promote tumor angiogenesis by production of several angiogenic factors. Identification of eosinophils in the inflammatory stroma has been proven to be an important prognosticator in cancers of mouth, oesophagus, larynx, pharynx, breast, lung, and intestine. Therefore, the study aimed to correlate TATE with clinical and histopathological variables, and blood eosinophil count to assess the role of TATE as a prognosticator in Oral Squamous Cell Carcinoma (OSCC). Methods: Seventy two biopsy-proven cases of OSCC formed the study cohort. Blood eosinophil counts and TNM stage were obtained from the medical records. Tissue sections (5µm thick) were stained with Haematoxylin and Eosin. The eosinophils were quantified at invasive tumour front (ITF) in 10HPF (40x magnification) with an ocular grid. Bryne’s grading of ITF was also performed. A subset of thirty cases was also assessed for association of TATE with recurrence, involvement of lymph nodes and surgical margins. Results: 1) No statistically significant correlation was found between TATE and TNM stage, blood eosinophil counts and most parameters of Bryne’s grading system. 2) Statistically significant relation of intense degree of TATE was associated with the absence of distant metastasis, increased lympho-plasmacytic response and increased survival (diseasefree and overall) of OSCC patients. 3) In the subset of 30 cases, tissue eosinophil counts were higher in cases with lymph node involvement, decreased survival, without margin involvement and in cases that did not recur. Conclusion: While the role of eosinophils in mediating immune responses seems ambiguous as eosinophils support cell-mediated tumour immunity in early stages while inhibiting the same in advanced stages, TATE may be used as a surrogate marker for determination of prognosis in oral squamous cell carcinoma.

Keywords: tumour-associated tissue eosinophilia, oral squamous cell carcinoma, prognosticator, tumoral immunity

Procedia PDF Downloads 216
22 Coalescence of Insulin and Triglyceride/High Density Lipoprotein Cholesterol Ratio for the Derivation of a Laboratory Index to Predict Metabolic Syndrome in Morbid Obese Children

Authors: Orkide Donma, Mustafa M. Donma

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Morbid obesity is a health threatening condition particularly in children. Generally, it leads to the development of metabolic syndrome (MetS) characterized by central obesity, elevated fasting blood glucose (FBG), triglyceride (TRG), blood pressure values and suppressed high density lipoprotein cholesterol (HDL-C) levels. However, some ambiguities exist during the diagnosis of MetS in children below 10 years of age. Therefore, clinicians are in the need of some surrogate markers for the laboratory assessment of pediatric MetS. In this study, the aim is to develop an index, which will be more helpful during the evaluation of further risks detected in morbid obese (MO) children. A total of 235 children with normal body mass index (N-BMI), with varying degrees of obesity; overweight (OW), obese (OB), MO as well as MetS participated in this study. The study was approved by the Institutional Ethical Committee. Informed consent forms were obtained from the parents of the children. Obesity states of the children were classified using BMI percentiles adjusted for age and sex. For the purpose, tabulated data prepared by WHO were used. MetS criteria were defined. Systolic and diastolic blood pressure values were measured. Parameters related to glucose and lipid metabolisms were determined. FBG, insulin (INS), HDL-C, TRG concentrations were determined. Diagnostic Obesity Notation Model Assessment Laboratory (DONMALAB) Index [ln TRG/HDL-C*INS] was introduced. Commonly used insulin resistance (IR) indices such as Homeostatic Model Assessment for IR (HOMA-IR) as well as ratios such as TRG/HDL-C, TRG/HDL-C*INS, HDL-C/TRG*INS, TRG/HDL-C*INS/FBG, log, and ln versions of these ratios were calculated. Results were interpreted using statistical package program (SPSS Version 16.0) for Windows. The data were evaluated using appropriate statistical tests. The degree for statistical significance was defined as 0.05. 35 N, 20 OW, 47 OB, 97 MO children and 36 with MetS were investigated. Mean ± SD values of TRG/HDL-C were 1.27 ± 0.69, 1.86 ± 1.08, 2.15 ± 1.22, 2.48 ± 2.35 and 4.61 ± 3.92 for N, OW, OB, MO and MetS children, respectively. Corresponding values for the DONMALAB index were 2.17 ± 1.07, 3.01 ± 0.94, 3.41 ± 0.93, 3.43 ± 1.08 and 4.32 ± 1.00. TRG/HDL-C ratio significantly differed between N and MetS groups. On the other hand, DONMALAB index exhibited statistically significant differences between N and all the other groups except the OW group. This index was capable of discriminating MO children from those with MetS. Statistically significant elevations were detected in MO children with MetS (p < 0.05). Multiple parameters are commonly used during the assessment of MetS. Upon evaluation of the values obtained for N, OW, OB, MO groups and for MO children with MetS, the [ln TRG/HDL-C*INS] value was unique in discriminating children with MetS.

Keywords: children, index, laboratory, metabolic syndrome, obesity

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21 Study into the Interactions of Primary Limbal Epithelial Stem Cells and HTCEPI Using Tissue Engineered Cornea

Authors: Masoud Sakhinia, Sajjad Ahmad

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Introduction: Though knowledge of the compositional makeup and structure of the limbal niche has progressed exponentially during the past decade, much is yet to be understood. Identifying the precise profile and role of the stromal makeup which spans the ocular surface may inform researchers of the most optimum conditions needed to effectively expand LESCs in vitro, whilst preserving their differentiation status and phenotype. Limbal fibroblasts, as opposed to corneal fibroblasts are thought to form an important component of the microenvironment where LESCs reside. Methods: The corneal stroma was tissue engineered in vitro using both limbal and corneal fibroblasts embedded within a tissue engineered 3D collagen matrix. The effect of these two different fibroblasts on LESCs and hTCEpi corneal epithelial cell line were then subsequently determined using phase contrast microscopy, histolological analysis and PCR for specific stem cell markers. The study aimed to develop an in vitro model which could be used to determine whether limbal, as opposed to corneal fibroblasts, maintained the stem cell phenotype of LESCs and hTCEpi cell line. Results: Tissue culture analysis was inconclusive and required further quantitative analysis for remarks on cell proliferation within the varying stroma. Histological analysis of the tissue-engineered cornea showed a comparable structure to that of the human cornea, though with limited epithelial stratification. PCR results for epithelial cell markers of cells cultured on limbal fibroblasts showed reduced expression of CK3, a negative marker for LESC’s, whilst also exhibiting a relatively low expression level of P63, a marker for undifferentiated LESCs. Conclusion: We have shown the potential for the construction of a tissue engineered human cornea using a 3D collagen matrix and described some preliminary results in the analysis of the effects of varying stroma consisting of limbal and corneal fibroblasts, respectively, on the proliferation of stem cell phenotype of primary LESCs and hTCEpi corneal epithelial cells. Although no definitive marker exists to conclusively illustrate the presence of LESCs, the combination of positive and negative stem cell markers in our study were inconclusive. Though it is less traslational to the human corneal model, the use of conditioned medium from that of limbal and corneal fibroblasts may provide a more simple avenue. Moreover, combinations of extracellular matrices could be used as a surrogate in these culture models.

Keywords: cornea, Limbal Stem Cells, tissue engineering, PCR

Procedia PDF Downloads 250
20 Assessment of Bisphenol A and 17 α-Ethinyl Estradiol Bioavailability in Soils Treated with Biosolids

Authors: I. Ahumada, L. Ascar, C. Pedraza, J. Montecino

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It has been found that the addition of biosolids to soil is beneficial to soil health, enriching soil with essential nutrient elements. Although this sludge has properties that allow for the improvement of the physical features and productivity of agricultural and forest soils and the recovery of degraded soils, they also contain trace elements, organic trace and pathogens that can cause damage to the environment. The application of these biosolids to land without the total reclamation and the treated wastewater can transfer these compounds into terrestrial and aquatic environments, giving rise to potential accumulation in plants. The general aim of this study was to evaluate the bioavailability of bisphenol A (BPA), and 17 α-ethynyl estradiol (EE2) in a soil-biosolid system using wheat (Triticum aestivum) plant assays and a predictive extraction method using a solution of hydroxypropyl-β-cyclodextrin (HPCD) to determine if it is a reliable surrogate for this bioassay. Two soils were obtained from the central region of Chile (Lo Prado and Chicauma). Biosolids were obtained from a regional wastewater treatment plant. The soils were amended with biosolids at 90 Mg ha-1. Soils treated with biosolids, spiked with 10 mgkg-1 of the EE2 and 15 mgkg-1 and 30 mgkg-1of BPA were also included. The BPA, and EE2 concentration were determined in biosolids, soils and plant samples through ultrasound assisted extraction, solid phase extraction (SPE) and gas chromatography coupled to mass spectrometry determination (GC/MS). The bioavailable fraction found of each one of soils cultivated with wheat plants was compared with results obtained through a cyclodextrin biosimulator method. The total concentration found in biosolid from a treatment plant was 0.150 ± 0.064 mgkg-1 and 12.8±2.9 mgkg-1 of EE2 and BPA respectively. BPA and EE2 bioavailability is affected by the organic matter content and the physical and chemical properties of the soil. The bioavailability response of both compounds in the two soils varied with the EE2 and BPA concentration. It was observed in the case of EE2, the bioavailability in wheat plant crops contained higher concentrations in the roots than in the shoots. The concentration of EE2 increased with increasing biosolids rate. On the other hand, for BPA, a higher concentration was found in the shoot than the roots of the plants. The predictive capability the HPCD extraction was assessed using a simple linear correlation test, for both compounds in wheat plants. The correlation coefficients for the EE2 obtained from the HPCD extraction with those obtained from the wheat plants were r= 0.99 and p-value ≤ 0.05. On the other hand, in the case of BPA a correlation was not found. Therefore, the methodology was validated with respect to wheat plants bioassays, only in the EE2 case. Acknowledgments: The authors thank FONDECYT 1150502.

Keywords: emerging compounds, bioavailability, biosolids, endocrine disruptors

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19 A Method against Obsolescence of Three-Dimensional Archaeological Collection. Two Cases of Study from Qubbet El-Hawa Necropolis, Aswan, Egypt

Authors: L. Serrano-Lara, J.M Alba-Gómez

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Qubbet el–Hawa Project has been documented archaeological artifacts as 3d models by laser scanning technique since 2015. Currently, research has obtained the right methodology to develop a high accuracy photographic texture for each geometrical 3D model. Furthermore, the right methodology to attach the complete digital surrogate into a 3DPDF document has been obtained; it is used as a catalogue worksheet that brings archaeological data and, at the same time, allows us to obtain precise measurements, volume calculations and cross-section mapping of each scanned artifact. This validated archaeological documentation is the first step for dissemination, application as Qubbet el-Hawa Virtual Museum, and, moreover, multi-sensory experience through 3D print archaeological artifacts. Material culture from four funerary complexes constructed in West Aswan has become physical replicas opening the archaeological research process itself and offering creative possibilities on museology or educational projects. This paper shares a method of acquiring texture for scanning´s output product in order to achieve a 3DPDF archaeological cataloguing, and, on the other hand, to allow the colorfully 3D printing of singular archaeological artifacts. The proposed method has undergone two concrete cases, a polychrome wooden ushabti, and, a cartonnage mask belonging to a lady, bought recovered on intact tomb QH34aa. Both 3D model results have been implemented on three main applications, archaeological 3D catalogue, public dissemination activities, and the 3D artifact model in a bachelor education program. Due to those three already mentioned applications, productive interaction among spectator and three-dimensional artifact have been increased; moreover, functionality as archaeological documentation has been consolidated. Finding the right methodology to assign a specific color to each vector on the geometric 3D model, we had been achieved two essential archaeological applications. Firstly, 3DPDF as a display document for an archaeological catalogue, secondly, the possibility to obtain a colored 3d printed object to be displayed in public exhibitions. Obsolescences 3D models have become updated archaeological documentation of QH43aa tomb cultural material. Therefore, Qubbet el-Hawa Project has been actualized the educational potential of its results thanks to a multi-sensory experience that arose from 3d scanned´s archaeological artifacts.

Keywords: 3D printed, 3D scanner, Middle Kingdom, Qubbet el-Hawa necropolis, virtual archaeology

Procedia PDF Downloads 107
18 Platelet Volume Indices: Emerging Markers of Diabetic Thrombocytopathy

Authors: Mitakshara Sharma, S. K. Nema

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Diabetes mellitus (DM) is metabolic disorder prevalent in pandemic proportions, incurring significant morbidity and mortality due to associated vascular angiopathies. Platelet related thrombogenesis plays key role in pathogenesis of these complications. Most patients with type II DM suffer from preventable vascular complications and early diagnosis can help manage these successfully. These complications are attributed to platelet activation which can be recognised by the increase in Platelet Volume Indices(PVI) viz. Mean Platelet Volume(MPV) and Platelet Distribution Width(PDW). This study was undertaken with the aim of finding a relationship between PVI and vascular complications of Diabetes mellitus, their importance as a causal factor in these complications and use as markers for early detection of impending vascular complications in patients with poor glycaemic status. This is a cross-sectional study conducted for 2 years with total 930 subjects. The subjects were segregated in 03 groups on basis of glycosylated haemoglobin (HbA1C) as: - (a) Diabetic, (b) Non-Diabetic and (c) Subjects with Impaired fasting glucose(IFG) with 300 individuals in IFG and non-diabetic group & 330 individuals in diabetic group. The diabetic group was further divided into two groups: - (a) Diabetic subjects with diabetes related vascular complications (b) Diabetic subjects without diabetes related vascular complications. Samples for HbA1C and platelet indices were collected using Ethylene diamine tetracetic acid(EDTA) as anticoagulant and processed on SYSMEX-XS-800i autoanalyser. The study revealed stepwise increase in PVI from non-diabetics to IFG to diabetics. MPV and PDW of diabetics, IFG and non diabetics were 17.60 ± 2.04, 11.76 ± 0.73, 9.93 ± 0.64 and 19.17 ± 1.48, 15.49 ± 0.67, 10.59 ± 0.67 respectively with a significant p value 0.00 and a significant positive correlation (MPV-HbA1c r = 0.951; PDW-HbA1c r = 0.875). However, significant negative correlation was found between glycaemic levels and total platelet count (PC- HbA1c r =-0.164). MPV & PDW of subjects with and without diabetes related complications were (15.14 ± 1.04) fl & (17.51±0.39) fl and (18.96 ± 0.83) fl & (20.09 ± 0.98) fl respectively with a significant p value 0.00.The current study demonstrates raised platelet indices & reduced platelet counts in association with rising glycaemic levels and diabetes related vascular complications across various study groups & showed that platelet morphology is altered with increasing glycaemic levels. These changes can be known by measurements of PVI which are important, simple, cost effective, effortless tool & indicators of impending vascular complications in patients with deranged glycaemic control. PVI should be researched and explored further as surrogate markers to develop a clinical tool for early recognition of vascular changes related to diabetes and thereby help prevent them. They can prove to be more useful in developing countries with limited resources. This study is multi-parameter, comprehensive with adequately powered study design and represents pioneering effort in India on account of the fact that both Platelet indices (MPV & PDW) along with platelet count have been evaluated together for the first time in Diabetics, non diabetics, patients with IFG and also in the diabetic patients with and without diabetes related vascular complications.

Keywords: diabetes, HbA1C, IFG, MPV, PDW, PVI

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17 Comparison of Extracellular miRNA from Different Lymphocyte Cell Lines and Isolation Methods

Authors: Christelle E. Chua, Alicia L. Ho

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The development of a panel of differential gene expression signatures has been of interest in the field of biomarker discovery for radiation exposure. In the absence of the availability of exposed human subjects, lymphocyte cell lines have often been used as a surrogate to human whole blood, when performing ex vivo irradiation studies. The extent of variation between different lymphocyte cell lines is currently unclear, especially with regard to the expression of extracellular miRNA. This study compares the expression profile of extracellular miRNA isolated from different lymphocyte cell lines. It also compares the profile of miRNA obtained when different exosome isolation kits are used. Lymphocyte cell lines were created using lymphocytes isolated from healthy adult males of similar racial descent (Chinese American and Chinese Singaporean) and immortalised with Epstein-Barr virus. The cell lines were cultured in exosome-free cell culture media for 72h and the cell culture supernatant was removed for exosome isolation. Two exosome isolation kits were used. Total exosome isolation reagent (TEIR, ThermoFisher) is a polyethylene glycol (PEG)-based exosome precipitation kit, while ExoSpin (ES, Cell Guidance Systems) is a PEG-based exosome precipitation kit that includes an additional size exclusion chromatography step. miRNA from the isolated exosomes were isolated using miRNEASY minikit (Qiagen) and analysed using nCounter miRNA assay (Nanostring). Principal component analysis (PCA) results suggested that the overall extracellular miRNA expression profile differed between the lymphocyte cell line originating from the Chinese American donor and the cell line originating from the Chinese Singaporean donor. As the gender, age and racial origins of both donors are similar, this may suggest that there are other genetic or epigenetic differences that account for the variation in extracellular miRNA gene expression in lymphocyte cell lines. However, statistical analysis showed that only 3 miRNA genes had a fold difference > 2 at p < 0.05, suggesting that the differences may not be of that great a significance as to impact overall conclusions drawn from different cell lines. Subsequent analysis using cell lines from other donors will give further insight into the reproducibility of results when difference cell lines are used. PCA results also suggested that the method of exosome isolation impacted the expression profile. 107 miRNA had a fold difference > 2 at p < 0.05. This suggests that the inclusion of an additional size exclusion chromatography step altered the subset of the extracellular vesicles that were isolated. In conclusion, these results suggest that extracellular miRNA can be isolated and analysed from exosomes derived from lymphocyte cell lines. However, care must be taken in the choice of cell line and method of exosome isolation used.

Keywords: biomarker, extracellular miRNA, isolation methods, lymphocyte cell line

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16 Ex-vivo Bio-distribution Studies of a Potential Lung Perfusion Agent

Authors: Shabnam Sarwar, Franck Lacoeuille, Nadia Withofs, Roland Hustinx

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After the development of a potential surrogate of MAA, and its successful application for the diagnosis of pulmonary embolism in artificially embolized rats’ lungs, this microparticulate system were radiolabelled with gallium-68 to synthesize 68Ga-SBMP with high radiochemical purity >99%. As a prerequisite step of clinical trials, 68Ga- labelled starch based microparticles (SBMP) were analysed for their in-vivo behavior in small animals. The purpose of the presented work includes the ex-vivo biodistribution studies of 68Ga-SBMP in order to assess the activity uptake in target organs with respect to time, excretion pathways of the radiopharmaceutical, %ID/g in major organs, T/NT ratios, in-vivo stability of the radiotracer and subsequently the microparticles in the target organs. Radiolabelling of starch based microparticles was performed by incubating it with 68Ga generator eluate (430±26 MBq) at room temperature and pressure without using any harsh reaction condition. For Ex-vivo biodistribution studies healthy White Wistar rats weighing between 345-460 g were injected intravenously 68Ga-SBMP 20±8 MBq, containing about 2,00,000-6,00,000 SBMP particles in a volume of 700µL. The rats were euthanized at predefined time intervals (5min, 30min, 60min and 120min) and their organ parts were cut, washed, and put in the pre-weighed tubes and measured for radioactivity counts through automatic Gamma counter. The 68Ga-SBMP produced >99% RCP just after 10-20 min incubation through a simple and robust procedure. Biodistribution of 68Ga-SBMP showed that initially just after 5 min post injection major uptake was observed in the lungs following by blood, heart, liver, kidneys, bladder, urine, spleen, stomach, small intestine, colon, skin and skeleton, thymus and at last the smallest activity was found in brain. Radioactivity counts stayed stable in lungs with gradual decrease with the passage of time, and after 2h post injection, almost half of the activity were seen in lungs. This is a sufficient time to perform PET/CT lungs scanning in humans while activity in the liver, spleen, gut and urinary system decreased with time. The results showed that urinary system is the excretion pathways instead of hepatobiliary excretion. There was a high value of T/NT ratios which suggest fine tune images for PET/CT lung perfusion studies henceforth further pre-clinical studies and then clinical trials should be planned in order to utilize this potential lung perfusion agent.

Keywords: starch based microparticles, gallium-68, biodistribution, target organs, excretion pathways

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15 A Methodology of Using Fuzzy Logics and Data Analytics to Estimate the Life Cycle Indicators of Solar Photovoltaics

Authors: Thor Alexis Sazon, Alexander Guzman-Urbina, Yasuhiro Fukushima

Abstract:

This study outlines the method of how to develop a surrogate life cycle model based on fuzzy logic using three fuzzy inference methods: (1) the conventional Fuzzy Inference System (FIS), (2) the hybrid system of Data Analytics and Fuzzy Inference (DAFIS), which uses data clustering for defining the membership functions, and (3) the Adaptive-Neuro Fuzzy Inference System (ANFIS), a combination of fuzzy inference and artificial neural network. These methods were demonstrated with a case study where the Global Warming Potential (GWP) and the Levelized Cost of Energy (LCOE) of solar photovoltaic (PV) were estimated using Solar Irradiation, Module Efficiency, and Performance Ratio as inputs. The effects of using different fuzzy inference types, either Sugeno- or Mamdani-type, and of changing the number of input membership functions to the error between the calibration data and the model-generated outputs were also illustrated. The solution spaces of the three methods were consequently examined with a sensitivity analysis. ANFIS exhibited the lowest error while DAFIS gave slightly lower errors compared to FIS. Increasing the number of input membership functions helped with error reduction in some cases but, at times, resulted in the opposite. Sugeno-type models gave errors that are slightly lower than those of the Mamdani-type. While ANFIS is superior in terms of error minimization, it could generate solutions that are questionable, i.e. the negative GWP values of the Solar PV system when the inputs were all at the upper end of their range. This shows that the applicability of the ANFIS models highly depends on the range of cases at which it was calibrated. FIS and DAFIS generated more intuitive trends in the sensitivity runs. DAFIS demonstrated an optimal design point wherein increasing the input values does not improve the GWP and LCOE anymore. In the absence of data that could be used for calibration, conventional FIS presents a knowledge-based model that could be used for prediction. In the PV case study, conventional FIS generated errors that are just slightly higher than those of DAFIS. The inherent complexity of a Life Cycle study often hinders its widespread use in the industry and policy-making sectors. While the methodology does not guarantee a more accurate result compared to those generated by the Life Cycle Methodology, it does provide a relatively simpler way of generating knowledge- and data-based estimates that could be used during the initial design of a system.

Keywords: solar photovoltaic, fuzzy logic, inference system, artificial neural networks

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