Search results for: David Pérez
108 Preoperative Anxiety Evaluation: Comparing the Visual Facial Anxiety Scale/Yumul Faces Anxiety Scale, Numerical Verbal Rating Scale, Categorization Scale, and the State-Trait Anxiety Inventory
Authors: Roya Yumul, Chse, Ofelia Loani Elvir Lazo, David Chernobylsky, Omar Durra
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Background: Preoperative anxiety has been shown to be caused by the fear associated with surgical and anesthetic complications; however, the current gold standard for assessing patient anxiety, the STAI, is problematic to use in the preoperative setting given the duration and concentration required to complete the 40-item extensive questionnaire. Our primary aim in the study is to investigate the correlation of the Visual Facial Anxiety Scale (VFAS) and Numerical Verbal Rating Scale (NVRS) to State-Trait Anxiety Inventory (STAI) to determine the optimal anxiety scale to use in the perioperative setting. Methods: A clinical study of patients undergoing various surgeries was conducted utilizing each of the preoperative anxiety scales. Inclusion criteria included patients undergoing elective surgeries, while exclusion criteria included patients with anesthesia contraindications, inability to comprehend instructions, impaired judgement, substance abuse history, and those pregnant or lactating. 293 patients were analyzed in terms of demographics, anxiety scale survey results, and anesthesia data via Spearman Coefficients, Chi-Squared Analysis, and Fischer’s exact test utilized for comparison analysis. Results: Statistical analysis showed that VFAS had a higher correlation to STAI than NVRS (rs=0.66, p<0.0001 vs. rs=0.64, p<0.0001). The combined VFAS-Categorization Scores showed the highest correlation with the gold standard (rs=0.72, p<0.0001). Subgroup analysis showed similar results. STAI evaluation time (247.7 ± 54.81 sec) far exceeds VFAS (7.29 ± 1.61 sec), NVRS (7.23 ± 1.60 sec), and Categorization scales (7.29 ± 1.99 sec). Patients preferred VFAS (54.4%), Categorization (11.6%), and NVRS (8.8%). Anesthesiologists preferred VFAS (63.9%), NVRS (22.1%), and Categorization Scales (14.0%). Of note, the top five causes of preoperative anxiety were determined to be waiting (56.5%), pain (42.5%), family concerns (40.5%), no information about surgery (40.1%), or anesthesia (31.6%). Conclusions: Combined VFAS-Categorization Score (VCS) demonstrates the highest correlation to the gold standard, STAI. Both VFAS and Categorization tests also take significantly less time than STAI, which is critical in the preoperative setting. Among both patients and anesthesiologists, VFAS was the most preferred scale. This forms the basis of the Yumul FACES Anxiety Scale, designed for quick quantization and assessment in the preoperative setting while maintaining a high correlation to the golden standard. Additional studies using the formulated Yumul FACES Anxiety Scale are merited.Keywords: numerical verbal anxiety scale, preoperative anxiety, state-trait anxiety inventory, visual facial anxiety scale
Procedia PDF Downloads 139107 Getting to Know the Enemy: Utilization of Phone Record Analysis Simulations to Uncover a Target’s Personal Life Attributes
Authors: David S. Byrne
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The purpose of this paper is to understand how phone record analysis can enable identification of subjects in communication with a target of a terrorist plot. This study also sought to understand the advantages of the implementation of simulations to develop the skills of future intelligence analysts to enhance national security. Through the examination of phone reports which in essence consist of the call traffic of incoming and outgoing numbers (and not by listening to calls or reading the content of text messages), patterns can be uncovered that point toward members of a criminal group and activities planned. Through temporal and frequency analysis, conclusions were drawn to offer insights into the identity of participants and the potential scheme being undertaken. The challenge lies in the accurate identification of the users of the phones in contact with the target. Often investigators rely on proprietary databases and open sources to accomplish this task, however it is difficult to ascertain the accuracy of the information found. Thus, this paper poses two research questions: how effective are freely available web sources of information at determining the actual identification of callers? Secondly, does the identity of the callers enable an understanding of the lifestyle and habits of the target? The methodology for this research consisted of the analysis of the call detail records of the author’s personal phone activity spanning the period of a year combined with a hypothetical theory that the owner of said phone was a leader of terrorist cell. The goal was to reveal the identity of his accomplices and understand how his personal attributes can further paint a picture of the target’s intentions. The results of the study were interesting, nearly 80% of the calls were identified with over a 75% accuracy rating via datamining of open sources. The suspected terrorist’s inner circle was recognized including relatives and potential collaborators as well as financial institutions [money laundering], restaurants [meetings], a sporting goods store [purchase of supplies], and airline and hotels [travel itinerary]. The outcome of this research showed the benefits of cellphone analysis without more intrusive and time-consuming methodologies though it may be instrumental for potential surveillance, interviews, and developing probable cause for wiretaps. Furthermore, this research highlights the importance of building upon the skills of future intelligence analysts through phone record analysis via simulations; that hands-on learning in this case study emphasizes the development of the competencies necessary to improve investigations overall.Keywords: hands-on learning, intelligence analysis, intelligence education, phone record analysis, simulations
Procedia PDF Downloads 14106 Learning from Long COVID: How Healthcare Needs to Change for Contested Illnesses
Authors: David Tennison
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In the wake of the Covid-19 pandemic, a new chronic illness emerged onto the global stage: Long Covid. Long Covid presents with several symptoms commonly seen in other poorly-understood illnesses, such as fibromyalgia (FM) and myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS). However, while Long Covid has swiftly become a recognised illness, FM and ME/CFS are still seen as contested, which impacts patient care and healthcare experiences. This study aims to examine what the differences are between Long Covid and FM; and if the Long Covid case can provide guidance for how to address the healthcare challenge of contested illnesses. To address this question, this study performed comprehensive research into the history of FM; our current biomedical understanding of it; and available healthcare interventions (within the context of the UK NHS). Analysis was undertaken of the stigma and stereotypes around FM, and a comparison made between FM and the emerging Long Covid literature, along with the healthcare response to Long Covid. This study finds that healthcare for chronic contested illnesses in the UK is vastly insufficient - in terms of pharmaceutical and holistic interventions, and the provision of secondary care options. Interestingly, for Long Covid, many of the treatment suggestions are pulled directly from those used for contested illnesses. The key difference is in terms of funding and momentum – Long Covid has generated exponentially more interest and research in a short time than there has been in the last few decades of contested illness research. This stands to help people with FM and ME/CFS – for example, research has recently been funded into “brain fog”, a previously elusive and misunderstood symptom. FM is culturally regarded as a “women’s disease” and FM stigma stems from notions of “hysteria”. A key finding is that the idea of FM affecting women disproportionally is not reflected in modern population studies. Emerging data on Long Covid also suggests a slight leaning towards more female patients, however it is less feminised, potentially due to it emerging in the global historical moment of the pandemic. Another key difference is that FM is rated as an extremely low-prestige illness by healthcare professionals, while it was in large part due to the advocacy of affected healthcare professionals that Long Covid was so quickly recognised by science and medicine. In conclusion, Long Covid (and the risk of future pandemics and post-viral illnesses) highlight a crucial need for implementing new, and reinforcing existing, care networks for chronic illnesses. The difference in how contested illnesses like FM, and new ones like Long Covid are treated have a lot to do with the historical moment in which they emerge – but cultural stereotypes, from within and without medicine, need updating. Particularly as they contribute to disease stigma that causes genuine harm to patients. However, widespread understanding and acceptance of Long Covid could help fight contested illness stigma, and the attention, funding and research into Long Covid may actually help raise the profile of contested illnesses and uncover answers about their symptomatology.Keywords: long COVID, fibromyalgia, myalgic encephalomyelitis, chronic fatigue syndrome, NHS, healthcare, contested illnesses, chronic illnesses, COVID-19 pandemic
Procedia PDF Downloads 68105 Drug Delivery Cationic Nano-Containers Based on Pseudo-Proteins
Authors: Sophio Kobauri, Temur Kantaria, Nina Kulikova, David Tugushi, Ramaz Katsarava
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The elaboration of effective drug delivery vehicles is still topical nowadays since targeted drug delivery is one of the most important challenges of the modern nanomedicine. The last decade has witnessed enormous research focused on synthetic cationic polymers (CPs) due to their flexible properties, in particular as non-viral gene delivery systems, facile synthesis, robustness, not oncogenic and proven gene delivery efficiency. However, the toxicity is still an obstacle to the application in pharmacotherapy. For overcoming the problem, creation of new cationic compounds including the polymeric nano-size particles – nano-containers (NCs) loading with different pharmaceuticals and biologicals is still relevant. In this regard, a variety of NCs-based drug delivery systems have been developed. We have found that amino acid-based biodegradable polymers called as pseudo-proteins (PPs), which can be cleared from the body after the fulfillment of their function are highly suitable for designing pharmaceutical NCs. Among them, one of the most promising are NCs made of biodegradable Cationic PPs (CPPs). For preparing new cationic NCs (CNCs), we used CPPs composed of positively charged amino acid L-arginine (R). The CNCs were fabricated by two approaches using: (1) R-based homo-CPPs; (2) Blends of R-based CPPs with regular (neutral) PPs. According to the first approach NCs we prepared from CPPs 8R3 (composed of R, sebacic acid and 1,3-propanediol) and 8R6 (composed of R, sebacic acid and 1,6-hexanediol). The NCs prepared from these CPPs were 72-101 nm in size with zeta potential within +30 ÷ +35 mV at a concentration 6 mg/mL. According to the second approach, CPPs 8R6 was blended in organic phase with neutral PPs 8L6 (composed of leucine, sebacic acid and 1,6-hexanediol). The NCs prepared from the blends were 130-140 nm in size with zeta potential within +20 ÷ +28 mV depending on 8R6/8L6 ratio. The stability studies of fabricated NCs showed that no substantial change of the particle size and distribution and no big particles’ formation is observed after three months storage. In vitro biocompatibility study of the obtained NPs with four different stable cell lines: A549 (human), U-937 (human), RAW264.7 (murine), Hepa 1-6 (murine) showed both type cathionic NCs are biocompatible. The obtained data allow concluding that the obtained CNCs are promising for the application as biodegradable drug delivery vehicles. This work was supported by the joint grant from the Science and Technology Center in Ukraine and Shota Rustaveli National Science Foundation of Georgia #6298 'New biodegradable cationic polymers composed of arginine and spermine-versatile biomaterials for various biomedical applications'.Keywords: biodegradable polymers, cationic pseudo-proteins, nano-containers, drug delivery vehicles
Procedia PDF Downloads 154104 Recrystallization Behavior and Microstructural Evolution of Nickel Base Superalloy AD730 Billet during Hot Forging at Subsolvus Temperatures
Authors: Marcos Perez, Christian Dumont, Olivier Nodin, Sebastien Nouveau
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Nickel superalloys are used to manufacture high-temperature rotary engine parts such as high-pressure disks in gas turbine engines. High strength at high operating temperatures is required due to the levels of stress and heat the disk must withstand. Therefore it is necessary parts made from materials that can maintain mechanical strength at high temperatures whilst remain comparatively low in cost. A manufacturing process referred to as the triple melt process has made the production of cast and wrought (C&W) nickel superalloys possible. This means that the balance of cost and performance at high temperature may be optimized. AD730TM is a newly developed Ni-based superalloy for turbine disk applications, with reported superior service properties around 700°C when compared to Inconel 718 and several other alloys. The cast ingot is converted into billet during either cogging process or open die forging. The semi-finished billet is then further processed into its final geometry by forging, heat treating, and machining. Conventional ingot-to-billet conversion is an expensive and complex operation, requiring a significant amount of steps to break up the coarse as-cast structure and interdendritic regions. Due to the size of conventional ingots, it is difficult to achieve a uniformly high level of strain for recrystallization, resulting in non-recrystallized regions that retain large unrecrystallized grains. Non-uniform grain distributions will also affect the ultrasonic inspectability response, which is used to find defects in the final component. The main aim is to analyze the recrystallization behavior and microstructural evolution of AD730 at subsolvus temperatures from a semi-finished product (billet) under conditions representative of both cogging and hot forging operations. Special attention to the presence of large unrecrystallized grains was paid. Double truncated cones (DTCs) were hot forged at subsolvus temperatures in hydraulic press, followed by air cooling. SEM and EBSD analysis were conducted in the as-received (billet) and the as-forged conditions. AD730 from billet alloy presents a complex microstructure characterized by a mixture of several constituents. Large unrecrystallized grains present a substructure characterized by large misorientation gradients with the formation of medium to high angle boundaries in their interior, especially close to the grain boundaries, denoting inhomogeneous strain distribution. A fine distribution of intragranular precipitates was found in their interior, playing a key role on strain distribution and subsequent recrystallization behaviour during hot forging. Continuous dynamic recrystallization (CDRX) mechanism was found to be operating in the large unrecrystallized grains, promoting the formation intragranular DRX grains and the gradual recrystallization of these grains. Evidences that hetero-epitaxial recrystallization mechanism is operating in AD730 billet material were found. Coherent γ-shells around primary γ’ precipitates were found. However, no significant contribution to the overall recrystallization during hot forging was found. By contrast, strain presents the strongest effect on the microstructural evolution of AD730, increasing the recrystallization fraction and refining the structure. Regions with low level of deformation (ε ≤ 0.6) were translated into large fractions of unrecrystallized structures (strain accumulation). The presence of undissolved secondary γ’ precipitates (pinning effect), prior to hot forging operations, could explain these results.Keywords: AD730 alloy, continuous dynamic recrystallization, hot forging, γ’ precipitates
Procedia PDF Downloads 198103 Insect Manure (Frass) as a Complementary Fertilizer to Enhance Soil Mineralization Function: Application to Cranberry and Field Crops
Authors: Joël Passicousset, David Gilbert, Chloé Chervier-Legourd, Emmanuel Caron-Garant, Didier Labarre
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Living soil agriculture tries to reconciliate food production while improving soil health, soil biodiversity, soil fertility and more generally attenuating the inherent environmental drawbacks induced by modern agriculture. Using appropriate organic materials as soil amendments has a role to play in the aim of increasing the soil organic matter, improving soil fertility, sequestering carbon, and diminishing the dependence on both mineral fertilizer and pesticides. Insect farming consists in producing insects that can be used as a rich-in-protein and entomo-based food. Usually, detritivores are chosen, thus they can be fed with food wastes, which contributes to circular economy while producing low-carbon food. This process also produces frass, made of insect feces, exuvial material, and non-digested fibrous material, that have valuable fertilizer and biostimulation properties. But frass, used as a sole fertilizer on a crop may be not completely adequate for plants’ needs. This is why this project considers black soldier fly (termed BSF, one of the three main insect species grown commercially) frass as a complementary fertilizer, both in organic and in conventional contexts. Three kinds of experiments are made to understand the behaviour of fertilizer treatments based on frass incorporation. Lab-scale mineralization experiments suggest that BSF frass alone mineralizes more slowly than chicken manure alone (CM), but at a ratio of 90% CM-10% BSF frass, the mineralization rate of the mixture is higher than both frass and CM individually. For example, in the 7 days following the fertilization with same nitrogen amount introduced among treatments, around 80% of the nitrogen content supplied through 90% CM-10% BSF frass fertilization is present in the soil under mineral forms, compared to roughly 60% for commercial CM fertilization and 45% with BSF-frass. This suggests that BSF frass contains a more recalcitrant form of organic nitrogen than CM, but also that BSF frass has a highly active microbiota that can increase CM mineralization rate. Consequently, when progressive mineralization is needed, pure BSF-frass may be a consistent option from an agronomic aspect whereas, for specific crops that require spikes of readily available nitrogen sources (like cranberry), fast release 90CM-10BSF frass biofertilizer are more appropriate. Field experiments on cranberry suggests that, indeed, 90CM-10BSF frass is a potent candidate for organic cranberry production, as currently, organic growers rely solely on CM, whose mineralization kinetics are known to imperfectly match plant’s needs, which is known to be a major reason that sustains the current yield gap between conventional and organic cranberry sectors.Keywords: soil mineralization, biofertilizer, BSF-frass, chicken manure, soil functions, nitrogen, soil microbiota
Procedia PDF Downloads 69102 Comparison of the Yumul Faces Anxiety Scale to the Categorization Scale, the Numerical Verbal Rating Scale, and the State-Trait Anxiety Inventory for Preoperative Anxiety Evaluation
Authors: Ofelia Loani Elvir Lazo, Roya Yumul, David Chernobylsky, Omar Durra
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Background: It is crucial to detect the patient’s existing anxiety to assist patients in a perioperative setting which is to be caused by the fear associated with surgical and anesthetic complications. However, the current gold standard for assessing patient anxiety, the STAI, is problematic to use in the preoperative setting, given the duration and concentration required to complete the 40-item questionnaire. Our primary aim in the study is to investigate the correlation of the Yumul Visual Facial Anxiety Scale (VFAS) and Numerical Verbal Rating Scale (NVRS) to State-Trait Anxiety Inventory (STAI) to determine the optimal anxiety scale to use in the perioperative setting. Methods: A clinical study of patients undergoing various surgeries was conducted utilizing each of the preoperative anxiety scales. Inclusion criteria included patients undergoing elective surgeries, while exclusion criteria included patients with anesthesia contraindications, inability to comprehend instructions, impaired judgement, substance abuse history, and those pregnant or lactating. 293 patients were analyzed in terms of demographics, anxiety scale survey results, and anesthesia data via Spearman Coefficients, Chi-Squared Analysis, and Fischer’s exact test utilized for comparative analysis. Results: Statistical analysis showed that VFAS had a higher correlation to STAI than NVRS (rs=0.66, p<0.0001 vs. rs=0.64, p<0.0001). The combined VFAS-Categorization Scores showed the highest correlation with the gold standard (rs=0.72, p<0.0001). Subgroup analysis showed similar results. STAI evaluation time (247.7 ± 54.81 sec) far exceeds VFAS (7.29 ± 1.61 sec), NVRS (7.23 ± 1.60 sec), and Categorization scales (7.29 ± 1.99 sec). Patients preferred VFAS (54.4%), Categorization (11.6%), and NVRS (8.8%). Anesthesiologists preferred VFAS (63.9%), NVRS (22.1%), and Categorization Scales (14.0%). Of note, the top five causes of preoperative anxiety were determined to be waiting (56.5%), pain (42.5%), family concerns (40.5%), no information about surgery (40.1%), or anesthesia (31.6%). Conclusıons: Both VFAS and Categorization tests also take significantly less time than STAI, which is critical in the preoperative setting. Combined VFAS-Categorization Score (VCS) demonstrates the highest correlation to the gold standard, STAI. Among both patients and anesthesiologists, VFAS was the most preferred scale. This forms the basis of the Yumul Faces Anxiety Scale, designed for quick quantization and assessment in the preoperative setting while maintaining a high correlation to the golden standard. Additional studies using the formulated Yumul Faces Anxiety Scale are merited.Keywords: numerical verbal anxiety scale, preoperative anxiety, state-trait anxiety inventory, visual facial anxiety scale
Procedia PDF Downloads 116101 Design of a Low-Cost, Portable, Sensor Device for Longitudinal, At-Home Analysis of Gait and Balance
Authors: Claudia Norambuena, Myissa Weiss, Maria Ruiz Maya, Matthew Straley, Elijah Hammond, Benjamin Chesebrough, David Grow
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The purpose of this project is to develop a low-cost, portable sensor device that can be used at home for long-term analysis of gait and balance abnormalities. One area of particular concern involves the asymmetries in movement and balance that can accompany certain types of injuries and/or the associated devices used in the repair and rehabilitation process (e.g. the use of splints and casts) which can often increase chances of falls and additional injuries. This device has the capacity to monitor a patient during the rehabilitation process after injury or operation, increasing the patient’s access to healthcare while decreasing the number of visits to the patient’s clinician. The sensor device may thereby improve the quality of the patient’s care, particularly in rural areas where access to the clinician could be limited, while simultaneously decreasing the overall cost associated with the patient’s care. The device consists of nine interconnected accelerometer/ gyroscope/compass chips (9-DOF IMU, Adafruit, New York, NY). The sensors attach to and are used to determine the orientation and acceleration of the patient’s lower abdomen, C7 vertebra (lower neck), L1 vertebra (middle back), anterior side of each thigh and tibia, and dorsal side of each foot. In addition, pressure sensors are embedded in shoe inserts with one sensor (ESS301, Tekscan, Boston, MA) beneath the heel and three sensors (Interlink 402, Interlink Electronics, Westlake Village, CA) beneath the metatarsal bones of each foot. These sensors measure the distribution of the weight applied to each foot as well as stride duration. A small microntroller (Arduino Mega, Arduino, Ivrea, Italy) is used to collect data from these sensors in a CSV file. MATLAB is then used to analyze the data and output the hip, knee, ankle, and trunk angles projected on the sagittal plane. An open-source program Processing is then used to generate an animation of the patient’s gait. The accuracy of the sensors was validated through comparison to goniometric measurements (±2° error). The sensor device was also shown to have sufficient sensitivity to observe various gait abnormalities. Several patients used the sensor device, and the data collected from each represented the patient’s movements. Further, the sensors were found to have the ability to observe gait abnormalities caused by the addition of a small amount of weight (4.5 - 9.1 kg) to one side of the patient. The user-friendly interface and portability of the sensor device will help to construct a bridge between patients and their clinicians with fewer necessary inpatient visits.Keywords: biomedical sensing, gait analysis, outpatient, rehabilitation
Procedia PDF Downloads 286100 Modeling Engagement with Multimodal Multisensor Data: The Continuous Performance Test as an Objective Tool to Track Flow
Authors: Mohammad H. Taheri, David J. Brown, Nasser Sherkat
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Engagement is one of the most important factors in determining successful outcomes and deep learning in students. Existing approaches to detect student engagement involve periodic human observations that are subject to inter-rater reliability. Our solution uses real-time multimodal multisensor data labeled by objective performance outcomes to infer the engagement of students. The study involves four students with a combined diagnosis of cerebral palsy and a learning disability who took part in a 3-month trial over 59 sessions. Multimodal multisensor data were collected while they participated in a continuous performance test. Eye gaze, electroencephalogram, body pose, and interaction data were used to create a model of student engagement through objective labeling from the continuous performance test outcomes. In order to achieve this, a type of continuous performance test is introduced, the Seek-X type. Nine features were extracted including high-level handpicked compound features. Using leave-one-out cross-validation, a series of different machine learning approaches were evaluated. Overall, the random forest classification approach achieved the best classification results. Using random forest, 93.3% classification for engagement and 42.9% accuracy for disengagement were achieved. We compared these results to outcomes from different models: AdaBoost, decision tree, k-Nearest Neighbor, naïve Bayes, neural network, and support vector machine. We showed that using a multisensor approach achieved higher accuracy than using features from any reduced set of sensors. We found that using high-level handpicked features can improve the classification accuracy in every sensor mode. Our approach is robust to both sensor fallout and occlusions. The single most important sensor feature to the classification of engagement and distraction was shown to be eye gaze. It has been shown that we can accurately predict the level of engagement of students with learning disabilities in a real-time approach that is not subject to inter-rater reliability, human observation or reliant on a single mode of sensor input. This will help teachers design interventions for a heterogeneous group of students, where teachers cannot possibly attend to each of their individual needs. Our approach can be used to identify those with the greatest learning challenges so that all students are supported to reach their full potential.Keywords: affective computing in education, affect detection, continuous performance test, engagement, flow, HCI, interaction, learning disabilities, machine learning, multimodal, multisensor, physiological sensors, student engagement
Procedia PDF Downloads 9399 Neural Synchronization - The Brain’s Transfer of Sensory Data
Authors: David Edgar
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To understand how the brain’s subconscious and conscious functions, we must conquer the physics of Unity, which leads to duality’s algorithm. Where the subconscious (bottom-up) and conscious (top-down) processes function together to produce and consume intelligence, we use terms like ‘time is relative,’ but we really do understand the meaning. In the brain, there are different processes and, therefore, different observers. These different processes experience time at different rates. A sensory system such as the eyes cycles measurement around 33 milliseconds, the conscious process of the frontal lobe cycles at 300 milliseconds, and the subconscious process of the thalamus cycle at 5 milliseconds. Three different observers experience time differently. To bridge observers, the thalamus, which is the fastest of the processes, maintains a synchronous state and entangles the different components of the brain’s physical process. The entanglements form a synchronous cohesion between the brain components allowing them to share the same state and execute in the same measurement cycle. The thalamus uses the shared state to control the firing sequence of the brain’s linear subconscious process. Sharing state also allows the brain to cheat on the amount of sensory data that must be exchanged between components. Only unpredictable motion is transferred through the synchronous state because predictable motion already exists in the shared framework. The brain’s synchronous subconscious process is entirely based on energy conservation, where prediction regulates energy usage. So, the eyes every 33 milliseconds dump their sensory data into the thalamus every day. The thalamus is going to perform a motion measurement to identify the unpredictable motion in the sensory data. Here is the trick. The thalamus conducts its measurement based on the original observation time of the sensory system (33 ms), not its own process time (5 ms). This creates a data payload of synchronous motion that preserves the original sensory observation. Basically, a frozen moment in time (Flat 4D). The single moment in time can then be processed through the single state maintained by the synchronous process. Other processes, such as consciousness (300 ms), can interface with the synchronous state to generate awareness of that moment. Now, synchronous data traveling through a separate faster synchronous process creates a theoretical time tunnel where observation time is tunneled through the synchronous process and is reproduced on the other side in the original time-relativity. The synchronous process eliminates time dilation by simply removing itself from the equation so that its own process time does not alter the experience. To the original observer, the measurement appears to be instantaneous, but in the thalamus, a linear subconscious process generating sensory perception and thought production is being executed. It is all just occurring in the time available because other observation times are slower than thalamic measurement time. For life to exist in the physical universe requires a linear measurement process, it just hides by operating at a faster time relativity. What’s interesting is time dilation is not the problem; it’s the solution. Einstein said there was no universal time.Keywords: neural synchronization, natural intelligence, 99.95% IoT data transmission savings, artificial subconscious intelligence (ASI)
Procedia PDF Downloads 12398 Optimization of Operational Water Quality Parameters in a Drinking Water Distribution System Using Response Surface Methodology
Authors: Sina Moradi, Christopher W. K. Chow, John Van Leeuwen, David Cook, Mary Drikas, Patrick Hayde, Rose Amal
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Chloramine is commonly used as a disinfectant in drinking water distribution systems (DWDSs), particularly in Australia and the USA. Maintaining a chloramine residual throughout the DWDS is important in ensuring microbiologically safe water is supplied at the customer’s tap. In order to simulate how chloramine behaves when it moves through the distribution system, a water quality network model (WQNM) can be applied. In this work, the WQNM was based on mono-chloramine decomposition reactions, which enabled prediction of mono-chloramine residual at different locations through a DWDS in Australia, using the Bentley commercial hydraulic package (Water GEMS). The accuracy of WQNM predictions is influenced by a number of water quality parameters. Optimization of these parameters in order to obtain the closest results in comparison with actual measured data in a real DWDS would result in both cost reduction as well as reduction in consumption of valuable resources such as energy and materials. In this work, the optimum operating conditions of water quality parameters (i.e. temperature, pH, and initial mono-chloramine concentration) to maximize the accuracy of mono-chloramine residual predictions for two water supply scenarios in an entire network were determined using response surface methodology (RSM). To obtain feasible and economical water quality parameters for highest model predictability, Design Expert 8.0 software (Stat-Ease, Inc.) was applied to conduct the optimization of three independent water quality parameters. High and low levels of the water quality parameters were considered, inevitably, as explicit constraints, in order to avoid extrapolation. The independent variables were pH, temperature and initial mono-chloramine concentration. The lower and upper limits of each variable for two water supply scenarios were defined and the experimental levels for each variable were selected based on the actual conditions in studied DWDS. It was found that at pH of 7.75, temperature of 34.16 ºC, and initial mono-chloramine concentration of 3.89 (mg/L) during peak water supply patterns, root mean square error (RMSE) of WQNM for the whole network would be minimized to 0.189, and the optimum conditions for averaged water supply occurred at pH of 7.71, temperature of 18.12 ºC, and initial mono-chloramine concentration of 4.60 (mg/L). The proposed methodology to predict mono-chloramine residual can have a great potential for water treatment plant operators in accurately estimating the mono-chloramine residual through a water distribution network. Additional studies from other water distribution systems are warranted to confirm the applicability of the proposed methodology for other water samples.Keywords: chloramine decay, modelling, response surface methodology, water quality parameters
Procedia PDF Downloads 22497 Evolutionary Advantages of Loneliness with an Agent-Based Model
Authors: David Gottlieb, Jason Yoder
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The feeling of loneliness is not uncommon in modern society, and yet, there is a fundamental lack of understanding in its origins and purpose in nature. One interpretation of loneliness is that it is a subjective experience that punishes a lack of social behavior, and thus its emergence in human evolution is seemingly tied to the survival of early human tribes. Still, a common counterintuitive response to loneliness is a state of hypervigilance, resulting in social withdrawal, which may appear maladaptive to modern society. So far, no computational model of loneliness’ effect during evolution yet exists; however, agent-based models (ABM) can be used to investigate social behavior, and applying evolution to agents’ behaviors can demonstrate selective advantages for particular behaviors. We propose an ABM where each agent contains four social behaviors, and one goal-seeking behavior, letting evolution select the best behavioral patterns for resource allocation. In our paper, we use an algorithm similar to the boid model to guide the behavior of agents, but expand the set of rules that govern their behavior. While we use cohesion, separation, and alignment for simple social movement, our expanded model adds goal-oriented behavior, which is inspired by particle swarm optimization, such that agents move relative to their personal best position. Since agents are given the ability to form connections by interacting with each other, our final behavior guides agent movement toward its social connections. Finally, we introduce a mechanism to represent a state of loneliness, which engages when an agent's perceived social involvement does not meet its expected social involvement. This enables us to investigate a minimal model of loneliness, and using evolution we attempt to elucidate its value in human survival. Agents are placed in an environment in which they must acquire resources, as their fitness is based on the total resource collected. With these rules in place, we are able to run evolution under various conditions, including resource-rich environments, and when disease is present. Our simulations indicate that there is strong selection pressure for social behavior under circumstances where there is a clear discrepancy between initial resource locations, and against social behavior when disease is present, mirroring hypervigilance. This not only provides an explanation for the emergence of loneliness, but also reflects the diversity of response to loneliness in the real world. In addition, there is evidence of a richness of social behavior when loneliness was present. By introducing just two resource locations, we observed a divergence in social motivation after agents became lonely, where one agent learned to move to the other, who was in a better resource position. The results and ongoing work from this project show that it is possible to glean insight into the evolutionary advantages of even simple mechanisms of loneliness. The model we developed has produced unexpected results and has led to more questions, such as the impact loneliness would have at a larger scale, or the effect of creating a set of rules governing interaction beyond adjacency.Keywords: agent-based, behavior, evolution, loneliness, social
Procedia PDF Downloads 9496 Automated Computer-Vision Analysis Pipeline of Calcium Imaging Neuronal Network Activity Data
Authors: David Oluigbo, Erik Hemberg, Nathan Shwatal, Wenqi Ding, Yin Yuan, Susanna Mierau
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Introduction: Calcium imaging is an established technique in neuroscience research for detecting activity in neural networks. Bursts of action potentials in neurons lead to transient increases in intracellular calcium visualized with fluorescent indicators. Manual identification of cell bodies and their contours by experts typically takes 10-20 minutes per calcium imaging recording. Our aim, therefore, was to design an automated pipeline to facilitate and optimize calcium imaging data analysis. Our pipeline aims to accelerate cell body and contour identification and production of graphical representations reflecting changes in neuronal calcium-based fluorescence. Methods: We created a Python-based pipeline that uses OpenCV (a computer vision Python package) to accurately (1) detect neuron contours, (2) extract the mean fluorescence within the contour, and (3) identify transient changes in the fluorescence due to neuronal activity. The pipeline consisted of 3 Python scripts that could both be easily accessed through a Python Jupyter notebook. In total, we tested this pipeline on ten separate calcium imaging datasets from murine dissociate cortical cultures. We next compared our automated pipeline outputs with the outputs of manually labeled data for neuronal cell location and corresponding fluorescent times series generated by an expert neuroscientist. Results: Our results show that our automated pipeline efficiently pinpoints neuronal cell body location and neuronal contours and provides a graphical representation of neural network metrics accurately reflecting changes in neuronal calcium-based fluorescence. The pipeline detected the shape, area, and location of most neuronal cell body contours by using binary thresholding and grayscale image conversion to allow computer vision to better distinguish between cells and non-cells. Its results were also comparable to manually analyzed results but with significantly reduced result acquisition times of 2-5 minutes per recording versus 10-20 minutes per recording. Based on these findings, our next step is to precisely measure the specificity and sensitivity of the automated pipeline’s cell body and contour detection to extract more robust neural network metrics and dynamics. Conclusion: Our Python-based pipeline performed automated computer vision-based analysis of calcium image recordings from neuronal cell bodies in neuronal cell cultures. Our new goal is to improve cell body and contour detection to produce more robust, accurate neural network metrics and dynamic graphs.Keywords: calcium imaging, computer vision, neural activity, neural networks
Procedia PDF Downloads 8295 Violent, Psychological, Sexual and Abuse-Related Emergency Department Usage amongst Pediatric Victims of Physical Assault and Gun Violence: A Case-Control Study
Authors: Mary Elizabeth Bernardin, Margie Batek, Joseph Moen, David Schnadower
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Background: Injuries due to interpersonal violence are a common reason for emergency department (ED) visits amongst the American pediatric population. Gun violence, in particular, is associated with high morbidity, mortality as well as financial costs. Patterns of pediatric ED usage may be an indicator of risk for future violence, but very little data on the topic exists. Objective: The aims of this study were to assess for frequencies of ED usage for previous interpersonal violence, mental/behavioral issues, sexual/reproductive issues and concerns for abuse in youths presenting to EDs due to physical assault injuries (PAIs) compared to firearm injuries (FIs). Methods: In this retrospective case-control study, ED charts of children ages 8-19 years who presented with injuries due to interpersonal violent encounters from 2014-2017 were reviewed. Data was collected regarding all previous ED visits for injuries due to interpersonal violence (including physical assaults and firearm injuries), mental/behavioral health visits (including depression, suicidal ideation, suicide attempt, homicidal ideation and violent behavior), sexual/reproductive health visits (including sexually transmitted infections and pregnancy related issues), and concerns for abuse (including physical abuse or domestic violence, neglect, sexual abuse, sexual assault, and intimate partner violence). Logistic regression was used to identify predictors of gun violence based on previous ED visits amongst physical assault injured versus firearm injured youths. Results: A total of 407 patients presenting to the ED for an interpersonal violent encounter were analyzed, 251 (62%) of which were due to physical assault injuries (PAIs) and 156 (38%) due to firearm injuries (FIs). The majority of both PAI and FI patients had no previous history of ED visits for violence, mental/behavioral health, sexual/reproductive health or concern for abuse (60.8% PAI, 76.3% FI). 19.2% of PAI and 13.5% of FI youths had previous ED visits for physical assault injuries (OR 0.68, P=0.24, 95% CI 0.36 to 1.29). 1.6% of PAI and 3.2% of FI youths had a history of ED visits for previous firearm injuries (OR 3.6, P=0.34, 95% CI 0.04 to 2.95). 10% of PAI and 3.8% of FI youths had previous ED visits for mental/behavioral health issues (OR 0.91, P=0.80, 95% CI 0.43 to 1.93). 10% of PAI and 2.6% of FI youths had previous ED visits due to concerns for abuse (OR 0.76, P=0.55, 95% CI 0.31 to 1.86). Conclusions: There are no statistically significant differences between physical assault-injured and firearm-injured youths in terms of ED usage for previous violent injuries, mental/behavioral health visits, sexual/reproductive health visits or concerns for abuse. However, violently injured youths in this study have more than twice the number of previous ED usage for physical assaults and mental health visits than previous literature indicates. Data comparing ED usage of victims of interpersonal violence to nonviolent ED patients is needed, but this study supports the notion that EDs may be a useful place for identification of and enrollment in interventions for youths most at risk for future violence.Keywords: child abuse, emergency department usage, pediatric gun violence, pediatric interpersonal violence, pediatric mental health, pediatric reproductive health
Procedia PDF Downloads 23594 Metacognitive Processing in Early Readers: The Role of Metacognition in Monitoring Linguistic and Non-Linguistic Performance and Regulating Students' Learning
Authors: Ioanna Taouki, Marie Lallier, David Soto
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Metacognition refers to the capacity to reflect upon our own cognitive processes. Although there is an ongoing discussion in the literature on the role of metacognition in learning and academic achievement, little is known about its neurodevelopmental trajectories in early childhood, when children begin to receive formal education in reading. Here, we evaluate the metacognitive ability, estimated under a recently developed Signal Detection Theory model, of a cohort of children aged between 6 and 7 (N=60), who performed three two-alternative-forced-choice tasks (two linguistic: lexical decision task, visual attention span task, and one non-linguistic: emotion recognition task) including trial-by-trial confidence judgements. Our study has three aims. First, we investigated how metacognitive ability (i.e., how confidence ratings track accuracy in the task) relates to performance in general standardized tasks related to students' reading and general cognitive abilities using Spearman's and Bayesian correlation analysis. Second, we assessed whether or not young children recruit common mechanisms supporting metacognition across the different task domains or whether there is evidence for domain-specific metacognition at this early stage of development. This was done by examining correlations in metacognitive measures across different task domains and evaluating cross-task covariance by applying a hierarchical Bayesian model. Third, using robust linear regression and Bayesian regression models, we assessed whether metacognitive ability in this early stage is related to the longitudinal learning of children in a linguistic and a non-linguistic task. Notably, we did not observe any association between students’ reading skills and metacognitive processing in this early stage of reading acquisition. Some evidence consistent with domain-general metacognition was found, with significant positive correlations between metacognitive efficiency between lexical and emotion recognition tasks and substantial covariance indicated by the Bayesian model. However, no reliable correlations were found between metacognitive performance in the visual attention span and the remaining tasks. Remarkably, metacognitive ability significantly predicted children's learning in linguistic and non-linguistic domains a year later. These results suggest that metacognitive skill may be dissociated to some extent from general (i.e., language and attention) abilities and further stress the importance of creating educational programs that foster students’ metacognitive ability as a tool for long term learning. More research is crucial to understand whether these programs can enhance metacognitive ability as a transferable skill across distinct domains or whether unique domains should be targeted separately.Keywords: confidence ratings, development, metacognitive efficiency, reading acquisition
Procedia PDF Downloads 15093 Honneth, Feenberg, and the Redemption of Critical Theory of Technology
Authors: David Schafer
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Critical Theory is in sore need of a workable account of technology. It had one in the writings of Herbert Marcuse, or so it seemed until Jürgen Habermas mounted a critique in 'Technology and Science as Ideology' (Habermas, 1970) that decisively put it away. Ever since Marcuse’s work has been regarded outdated – a 'philosophy of consciousness' no longer seriously tenable. But with Marcuse’s view has gone the important insight that technology is no norm-free system (as Habermas portrays it) but can be laden with social bias. Andrew Feenberg is among a few serious scholars who have perceived this problem in post-Habermasian critical theory and has sought to revive a basically Marcusean account of technology. On his view, while so-called ‘technical elements’ that physically make up technologies are neutral with regard to social interests, there is a sense in which we may speak of a normative grammar or ‘technical code’ built-in to technology that can be socially biased in favor of certain groups over others (Feenberg, 2002). According to Feenberg, those perspectives on technology are reified which consider technology only by their technical elements to the neglect of their technical codes. Nevertheless, Feenberg’s account fails to explain what is normatively problematic with such reified views of technology. His plausible claim that they represent false perspectives on technology by itself does not explain how such views may be oppressive, even though Feenberg surely wants to be doing that stronger level of normative theorizing. Perceiving this deficit in his own account of reification, he tries to adopt Habermas’s version of systems-theory to ground his own critical theory of technology (Feenberg, 1999). But this is a curious move in light of Feenberg’s own legitimate critiques of Habermas’s portrayals of technology as reified or ‘norm-free.’ This paper argues that a better foundation may be found in Axel Honneth’s recent text, Freedom’s Right (Honneth, 2014). Though Honneth there says little explicitly about technology, he offers an implicit account of reification formulated in opposition to Habermas’s systems-theoretic approach. On this ‘normative functionalist’ account of reification, social spheres are reified when participants prioritize individualist ideals of freedom (moral and legal freedom) to the neglect of an intersubjective form of freedom-through-recognition that Honneth calls ‘social freedom.’ Such misprioritization is ultimately problematic because it is unsustainable: individual freedom is philosophically and institutionally dependent upon social freedom. The main difficulty in adopting Honneth’s social theory for the purposes of a theory of technology, however, is that the notion of social freedom is predicable only of social institutions, whereas it appears difficult to conceive of technology as an institution. Nevertheless, in light of Feenberg’s work, the idea that technology includes within itself a normative grammar (technical code) takes on much plausibility. To the extent that this normative grammar may be understood by the category of social freedom, Honneth’s dialectical account of the relationship between individual and social forms of freedom provides a more solid basis from which to ground the normative claims of Feenberg’s sociological account of technology than Habermas’s systems theory.Keywords: Habermas, Honneth, technology, Feenberg
Procedia PDF Downloads 19692 Development of an Automatic Computational Machine Learning Pipeline to Process Confocal Fluorescence Images for Virtual Cell Generation
Authors: Miguel Contreras, David Long, Will Bachman
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Background: Microscopy plays a central role in cell and developmental biology. In particular, fluorescence microscopy can be used to visualize specific cellular components and subsequently quantify their morphology through development of virtual-cell models for study of effects of mechanical forces on cells. However, there are challenges with these imaging experiments, which can make it difficult to quantify cell morphology: inconsistent results, time-consuming and potentially costly protocols, and limitation on number of labels due to spectral overlap. To address these challenges, the objective of this project is to develop an automatic computational machine learning pipeline to predict cellular components morphology for virtual-cell generation based on fluorescence cell membrane confocal z-stacks. Methods: Registered confocal z-stacks of nuclei and cell membrane of endothelial cells, consisting of 20 images each, were obtained from fluorescence confocal microscopy and normalized through software pipeline for each image to have a mean pixel intensity value of 0.5. An open source machine learning algorithm, originally developed to predict fluorescence labels on unlabeled transmitted light microscopy cell images, was trained using this set of normalized z-stacks on a single CPU machine. Through transfer learning, the algorithm used knowledge acquired from its previous training sessions to learn the new task. Once trained, the algorithm was used to predict morphology of nuclei using normalized cell membrane fluorescence images as input. Predictions were compared to the ground truth fluorescence nuclei images. Results: After one week of training, using one cell membrane z-stack (20 images) and corresponding nuclei label, results showed qualitatively good predictions on training set. The algorithm was able to accurately predict nuclei locations as well as shape when fed only fluorescence membrane images. Similar training sessions with improved membrane image quality, including clear lining and shape of the membrane, clearly showing the boundaries of each cell, proportionally improved nuclei predictions, reducing errors relative to ground truth. Discussion: These results show the potential of pre-trained machine learning algorithms to predict cell morphology using relatively small amounts of data and training time, eliminating the need of using multiple labels in immunofluorescence experiments. With further training, the algorithm is expected to predict different labels (e.g., focal-adhesion sites, cytoskeleton), which can be added to the automatic machine learning pipeline for direct input into Principal Component Analysis (PCA) for generation of virtual-cell mechanical models.Keywords: cell morphology prediction, computational machine learning, fluorescence microscopy, virtual-cell models
Procedia PDF Downloads 20391 The Confluence between Autism Spectrum Disorder and the Schizoid Personality
Authors: Murray David Schane
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Though years of clinical encounters with patients with autism spectrum disorders and those with a schizoid personality the many defining diagnostic features shared between these conditions have been explored and current neurobiological differences have been reviewed; and, critical and different treatment strategies for each have been devised. The paper compares and contrasts the apparent similarities between autism spectrum disorders and the schizoid personality are found in these DSM descriptive categories: restricted range of social-emotional reciprocity; poor non-verbal communicative behavior in social interactions; difficulty developing and maintaining relationships; detachment from social relationships; lack of the desire for or enjoyment of close relationships; and preference for solitary activities. In this paper autism, fundamentally a communicative disorder, is revealed to present clinically as a pervasive aversive response to efforts to engage with or be engaged by others. Autists with the Asperger presentation typically have language but have difficulty understanding humor, irony, sarcasm, metaphoric speech, and even narratives about social relationships. They also tend to seek sameness, possibly to avoid problems of social interpretation. Repetitive behaviors engage many autists as a screen against ambient noise, social activity, and challenging interactions. Also in this paper, the schizoid personality is revealed as a pattern of social avoidance, self-sufficiency and apparent indifference to others as a complex psychological defense against a deep, long-abiding fear of appropriation and perverse manipulation. Neither genetic nor MRI studies have yet located the explanatory data that identifies the cause or the neurobiology of autism. Similarly, studies of the schizoid have yet to group that condition with those found in schizophrenia. Through presentations of clinical examples, the treatment of autists of the Asperger type is revealed to address the autist’s extreme social aversion which also precludes the experience of empathy. Autists will be revealed as forming social attachments but without the capacity to interact with mutual concern. Empathy will be shown be teachable and, as social avoidance relents, understanding of the meaning and signs of empathic needs that autists can recognize and acknowledge. Treatment of schizoids will be shown to revolve around joining empathically with the schizoid’s apprehensions about interpersonal, interactive proximity. Models of both autism and schizoid personality traits have yet to be replicated in animals, thereby eliminating the role of translational research in providing the kind of clues to behavioral patterns that can be related to genetic, epigenetic and neurobiological measures. But as these clinical examples will attest, treatment strategies have significant impact.Keywords: autism spectrum, schizoid personality traits, neurobiological implications, critical diagnostic distinctions
Procedia PDF Downloads 11390 Assessment of Surface Water Quality near Landfill Sites Using a Water Pollution Index
Authors: Alejandro Cittadino, David Allende
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Landfilling of municipal solid waste is a common waste management practice in Argentina as in many parts of the world. There is extensive scientific literature on the potential negative effects of landfill leachates on the environment, so it’s necessary to be rigorous with the control and monitoring systems. Due to the specific municipal solid waste composition in Argentina, local landfill leachates contain large amounts of organic matter (biodegradable, but also refractory to biodegradation), as well as ammonia-nitrogen, small trace of some heavy metals, and inorganic salts. In order to investigate the surface water quality in the Reconquista river adjacent to the Norte III landfill, water samples both upstream and downstream the dumpsite are quarterly collected and analyzed for 43 parameters including organic matter, heavy metals, and inorganic salts, as required by the local standards. The objective of this study is to apply a water quality index that considers the leachate characteristics in order to determine the quality status of the watercourse through the landfill. The water pollution index method has been widely used in water quality assessments, particularly rivers, and it has played an increasingly important role in water resource management, since it provides a number simple enough for the public to understand, that states the overall water quality at a certain location and time. The chosen water quality index (ICA) is based on the values of six parameters: dissolved oxygen (in mg/l and percent saturation), temperature, biochemical oxygen demand (BOD5), ammonia-nitrogen and chloride (Cl-) concentration. The index 'ICA' was determined both upstream and downstream the Reconquista river, being the rating scale between 0 (very poor water quality) and 10 (excellent water quality). The monitoring results indicated that the water quality was unaffected by possible leachate runoff since the index scores upstream and downstream were ranked in the same category, although in general, most of the samples were classified as having poor water quality according to the index’s scale. The annual averaged ICA index scores (computed quarterly) were 4.9, 3.9, 4.4 and 5.0 upstream and 3.9, 5.0, 5.1 and 5.0 downstream the river during the study period between 2014 and 2017. Additionally, the water quality seemed to exhibit distinct seasonal variations, probably due to annual precipitation patterns in the study area. The ICA water quality index appears to be appropriate to evaluate landfill impacts since it accounts mainly for organic pollution and inorganic salts and the absence of heavy metals in the local leachate composition, however, the inclusion of other parameters could be more decisive in discerning the affected stream reaches from the landfill activities. A future work may consider adding to the index other parameters like total organic carbon (TOC) and total suspended solids (TSS) since they are present in the leachate in high concentrations.Keywords: landfill, leachate, surface water, water quality index
Procedia PDF Downloads 15089 Characterization of Thin Woven Composites Used in Printed Circuit Boards by Combining Numerical and Experimental Approaches
Authors: Gautier Girard, Marion Martiny, Sebastien Mercier, Mohamad Jrad, Mohamed-Slim Bahi, Laurent Bodin, Francois Lechleiter, David Nevo, Sophie Dareys
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Reliability of electronic devices has always been of highest interest for Aero-MIL and space applications. In any electronic device, Printed Circuit Board (PCB), providing interconnection between components, is a key for reliability. During the last decades, PCB technologies evolved to sustain and/or fulfill increased original equipment manufacturers requirements and specifications, higher densities and better performances, faster time to market and longer lifetime, newer material and mixed buildups. From the very beginning of the PCB industry up to recently, qualification, experiments and trials, and errors were the most popular methods to assess system (PCB) reliability. Nowadays OEM, PCB manufacturers and scientists are working together in a close relationship in order to develop predictive models for PCB reliability and lifetime. To achieve that goal, it is fundamental to characterize precisely base materials (laminates, electrolytic copper, …), in order to understand failure mechanisms and simulate PCB aging under environmental constraints by means of finite element method for example. The laminates are woven composites and have thus an orthotropic behaviour. The in-plane properties can be measured by combining classical uniaxial testing and digital image correlation. Nevertheless, the out-of-plane properties cannot be evaluated due to the thickness of the laminate (a few hundred of microns). It has to be noted that the knowledge of the out-of-plane properties is fundamental to investigate the lifetime of high density printed circuit boards. A homogenization method combining analytical and numerical approaches has been developed in order to obtain the complete elastic orthotropic behaviour of a woven composite from its precise 3D internal structure and its experimentally measured in-plane elastic properties. Since the mechanical properties of the resin surrounding the fibres are unknown, an inverse method is proposed to estimate it. The methodology has been applied to one laminate used in hyperfrequency spatial applications in order to get its elastic orthotropic behaviour at different temperatures in the range [-55°C; +125°C]. Next; numerical simulations of a plated through hole in a double sided PCB are performed. Results show the major importance of the out-of-plane properties and the temperature dependency of these properties on the lifetime of a printed circuit board. Acknowledgements—The support of the French ANR agency through the Labcom program ANR-14-LAB7-0003-01, support of CNES, Thales Alenia Space and Cimulec is acknowledged.Keywords: homogenization, orthotropic behaviour, printed circuit board, woven composites
Procedia PDF Downloads 20288 Development of Bilayer Coating System for Mitigating Corrosion of Offshore Wind Turbines
Authors: Adamantini Loukodimou, David Weston, Shiladitya Paul
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Offshore structures are subjected to harsh environments. It is documented that carbon steel needs protection from corrosion. The combined effect of UV radiation, seawater splash, and fluctuating temperatures diminish the integrity of these structures. In addition, the possibility of damage caused by floating ice, seaborne debris, and maintenance boats make them even more vulnerable. Their inspection and maintenance when far out in the sea are difficult, risky, and expensive. The most known method of mitigating corrosion of offshore structures is the use of cathodic protection. There are several zones in an offshore wind turbine. In the atmospheric zone, due to the lack of a continuous electrolyte (seawater) layer between the structure and the anode at all times, this method proves inefficient. Thus, the use of protective coatings becomes indispensable. This research focuses on the atmospheric zone. The conversion of commercially available and conventional paint (epoxy) system to an autonomous self-healing paint system via the addition of suitable encapsulated healing agents and catalyst is investigated in this work. These coating systems, which can self-heal when damaged, can provide a cost-effective engineering solution to corrosion and related problems. When the damage of the paint coating occurs, the microcapsules are designed to rupture and release the self-healing liquid (monomer), which then will react in the presence of the catalyst and solidify (polymerization), resulting in healing. The catalyst should be compatible with the system because otherwise, the self-healing process will not occur. The carbon steel substrate will be exposed to a corrosive environment, so the use of a sacrificial layer of Zn is also investigated. More specifically, the first layer of this new coating system will be TSZA (Thermally Sprayed Zn85/Al15) and will be applied on carbon steel samples with dimensions 100 x 150 mm after being blasted with alumina (size F24) as part of the surface preparation. Based on the literature, it corrodes readily, so one additional paint layer enriched with microcapsules will be added. Also, the reaction and the curing time are of high importance in order for this bilayer system of coating to work successfully. For the first experiments, polystyrene microcapsules loaded with 3-octanoyltio-1-propyltriethoxysilane were conducted. Electrochemical experiments such as Electrochemical Impedance Spectroscopy (EIS) confirmed the corrosion inhibiting properties of the silane. The diameter of the microcapsules was about 150-200 microns. Further experiments were conducted with different reagents and methods in order to obtain diameters of about 50 microns, and their self-healing properties were tested in synthetic seawater using electrochemical techniques. The use of combined paint/electrodeposited coatings allows for further novel development of composite coating systems. The potential for the application of these coatings in offshore structures will be discussed.Keywords: corrosion mitigation, microcapsules, offshore wind turbines, self-healing
Procedia PDF Downloads 11187 Finite Element Analysis of the Anaconda Device: Efficiently Predicting the Location and Shape of a Deployed Stent
Authors: Faidon Kyriakou, William Dempster, David Nash
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Abdominal Aortic Aneurysm (AAA) is a major life-threatening pathology for which modern approaches reduce the need for open surgery through the use of stenting. The success of stenting though is sometimes jeopardized by the final position of the stent graft inside the human artery which may result in migration, endoleaks or blood flow occlusion. Herein, a finite element (FE) model of the commercial medical device AnacondaTM (Vascutek, Terumo) has been developed and validated in order to create a numerical tool able to provide useful clinical insight before the surgical procedure takes place. The AnacondaTM device consists of a series of NiTi rings sewn onto woven polyester fabric, a structure that despite its column stiffness is flexible enough to be used in very tortuous geometries. For the purposes of this study, a FE model of the device was built in Abaqus® (version 6.13-2) with the combination of beam, shell and surface elements; the choice of these building blocks was made to keep the computational cost to a minimum. The validation of the numerical model was performed by comparing the deployed position of a full stent graft device inside a constructed AAA with a duplicate set-up in Abaqus®. Specifically, an AAA geometry was built in CAD software and included regions of both high and low tortuosity. Subsequently, the CAD model was 3D printed into a transparent aneurysm, and a stent was deployed in the lab following the steps of the clinical procedure. Images on the frontal and sagittal planes of the experiment allowed the comparison with the results of the numerical model. By overlapping the experimental and computational images, the mean and maximum distances between the rings of the two models were measured in the longitudinal, and the transverse direction and, a 5mm upper bound was set as a limit commonly used by clinicians when working with simulations. The two models showed very good agreement of their spatial positioning, especially in the less tortuous regions. As a result, and despite the inherent uncertainties of a surgical procedure, the FE model allows confidence that the final position of the stent graft, when deployed in vivo, can also be predicted with significant accuracy. Moreover, the numerical model run in just a few hours, an encouraging result for applications in the clinical routine. In conclusion, the efficient modelling of a complicated structure which combines thin scaffolding and fabric has been demonstrated to be feasible. Furthermore, the prediction capabilities of the location of each stent ring, as well as the global shape of the graft, has been shown. This can allow surgeons to better plan their procedures and medical device manufacturers to optimize their designs. The current model can further be used as a starting point for patient specific CFD analysis.Keywords: AAA, efficiency, finite element analysis, stent deployment
Procedia PDF Downloads 19086 Ecological and Historical Components of the Cultural Code of the City of Florence as Part of the Edutainment Project Velonotte International
Authors: Natalia Zhabo, Sergey Nikitin, Marina Avdonina, Mariya Nikitina
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The analysis of the activities of one of the events of the international educational and entertainment project Velonotte is provided: an evening bicycle tour with children around Florence. The aim of the project is to develop methods and techniques for increasing the sensitivity of the cycling participants and listeners of the radio broadcasts to the treasures of the national heritage, in this case, to the historical layers of the city and the ecology of the Renaissance epoch. The block of educational tasks is considered, and the issues of preserving the identity of the city are discussed. Methods. The Florentine event was prepared during more than a year. First of all the creative team selected such events of the history of the city which seem to be important for revealing the specifics of the city, its spirit - from antiquity to our days – including the forums of Internet with broad public opinion. Then a route (seven kilometers) was developed, which was proposed to the authorities and organizations of the city. The selection of speakers was conducted according to several criteria: they should be authors of books, famous scientists, connoisseurs in a certain sphere (toponymy, history of urban gardens, art history), capable and willing to talk with participants directly at the points of stops, in order to make a dialogue and so that performances could be organized with their participation. The music was chosen for each part of the itinerary to prepare the audience emotionally. Cards for coloring with images of the main content of each stop were created for children. A site was done to inform the participants and to keep photos, videos and the audio files with speakers’ speech afterward. Results: Held in April 2017, the event was dedicated to the 640th Anniversary of the Filippo Brunelleschi, Florentine architect, and to the 190th anniversary of the publication of Florence guide by Stendhal. It was supported by City of Florence and Florence Bike Festival. Florence was explored to transfer traditional elements of culture, sometimes unfairly forgotten from ancient times to Brunelleschi and Michelangelo and Tschaikovsky and David Bowie with lectures by professors of Universities. Memorable art boards were installed in public spaces. Elements of the cultural code are deeply internalized in the minds of the townspeople, the perception of the city in everyday life and human communication is comparable to such fundamental concepts of the self-awareness of the townspeople as mental comfort and the level of happiness. The format of a fun and playful walk with the ICT support gives new opportunities for enriching the city's cultural code of each citizen with new components, associations, connotations.Keywords: edutainment, cultural code, cycling, sensitization Florence
Procedia PDF Downloads 21985 Separating Landform from Noise in High-Resolution Digital Elevation Models through Scale-Adaptive Window-Based Regression
Authors: Anne M. Denton, Rahul Gomes, David W. Franzen
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High-resolution elevation data are becoming increasingly available, but typical approaches for computing topographic features, like slope and curvature, still assume small sliding windows, for example, of size 3x3. That means that the digital elevation model (DEM) has to be resampled to the scale of the landform features that are of interest. Any higher resolution is lost in this resampling. When the topographic features are computed through regression that is performed at the resolution of the original data, the accuracy can be much higher, and the reported result can be adjusted to the length scale that is relevant locally. Slope and variance are calculated for overlapping windows, meaning that one regression result is computed per raster point. The number of window centers per area is the same for the output as for the original DEM. Slope and variance are computed by performing regression on the points in the surrounding window. Such an approach is computationally feasible because of the additive nature of regression parameters and variance. Any doubling of window size in each direction only takes a single pass over the data, corresponding to a logarithmic scaling of the resulting algorithm as a function of the window size. Slope and variance are stored for each aggregation step, allowing the reported slope to be selected to minimize variance. The approach thereby adjusts the effective window size to the landform features that are characteristic to the area within the DEM. Starting with a window size of 2x2, each iteration aggregates 2x2 non-overlapping windows from the previous iteration. Regression results are stored for each iteration, and the slope at minimal variance is reported in the final result. As such, the reported slope is adjusted to the length scale that is characteristic of the landform locally. The length scale itself and the variance at that length scale are also visualized to aid in interpreting the results for slope. The relevant length scale is taken to be half of the window size of the window over which the minimum variance was achieved. The resulting process was evaluated for 1-meter DEM data and for artificial data that was constructed to have defined length scales and added noise. A comparison with ESRI ArcMap was performed and showed the potential of the proposed algorithm. The resolution of the resulting output is much higher and the slope and aspect much less affected by noise. Additionally, the algorithm adjusts to the scale of interest within the region of the image. These benefits are gained without additional computational cost in comparison with resampling the DEM and computing the slope over 3x3 images in ESRI ArcMap for each resolution. In summary, the proposed approach extracts slope and aspect of DEMs at the lengths scales that are characteristic locally. The result is of higher resolution and less affected by noise than existing techniques.Keywords: high resolution digital elevation models, multi-scale analysis, slope calculation, window-based regression
Procedia PDF Downloads 12684 Interacting with Multi-Scale Structures of Online Political Debates by Visualizing Phylomemies
Authors: Quentin Lobbe, David Chavalarias, Alexandre Delanoe
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The ICT revolution has given birth to an unprecedented world of digital traces and has impacted a wide number of knowledge-driven domains such as science, education or policy making. Nowadays, we are daily fueled by unlimited flows of articles, blogs, messages, tweets, etc. The internet itself can thus be considered as an unsteady hyper-textual environment where websites emerge and expand every day. But there are structures inside knowledge. A given text can always be studied in relation to others or in light of a specific socio-cultural context. By way of their textual traces, human beings are calling each other out: hypertext citations, retweets, vocabulary similarity, etc. We are in fact the architects of a giant web of elements of knowledge whose structures and shapes convey their own information. The global shapes of these digital traces represent a source of collective knowledge and the question of their visualization remains an opened challenge. How can we explore, browse and interact with such shapes? In order to navigate across these growing constellations of words and texts, interdisciplinary innovations are emerging at the crossroad between fields of social and computational sciences. In particular, complex systems approaches make it now possible to reconstruct the hidden structures of textual knowledge by means of multi-scale objects of research such as semantic maps and phylomemies. The phylomemy reconstruction is a generic method related to the co-word analysis framework. Phylomemies aim to reveal the temporal dynamics of large corpora of textual contents by performing inter-temporal matching on extracted knowledge domains in order to identify their conceptual lineages. This study aims to address the question of visualizing the global shapes of online political discussions related to the French presidential and legislative elections of 2017. We aim to build phylomemies on top of a dedicated collection of thousands of French political tweets enriched with archived contemporary news web articles. Our goal is to reconstruct the temporal evolution of online debates fueled by each political community during the elections. To that end, we want to introduce an iterative data exploration methodology implemented and tested within the free software Gargantext. There we combine synchronic and diachronic axis of visualization to reveal the dynamics of our corpora of tweets and web pages as well as their inner syntagmatic and paradigmatic relationships. In doing so, we aim to provide researchers with innovative methodological means to explore online semantic landscapes in a collaborative and reflective way.Keywords: online political debate, French election, hyper-text, phylomemy
Procedia PDF Downloads 18583 Sustainable Production of Pharmaceutical Compounds Using Plant Cell Culture
Authors: David A. Ullisch, Yantree D. Sankar-Thomas, Stefan Wilke, Thomas Selge, Matthias Pump, Thomas Leibold, Kai Schütte, Gilbert Gorr
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Plants have been considered as a source of natural substances for ages. Secondary metabolites from plants are utilized especially in medical applications but are more and more interesting as cosmetical ingredients and in the field of nutraceuticals. However, supply of compounds from natural harvest can be limited by numerous factors i.e. endangered species, low product content, climate impacts and cost intensive extraction. Especially in the pharmaceutical industry the ability to provide sufficient amounts of product and high quality are additional requirements which in some cases are difficult to fulfill by plant harvest. Whereas in many cases the complexity of secondary metabolites precludes chemical synthesis on a reasonable commercial basis, plant cells contain the biosynthetic pathway – a natural chemical factory – for a given compound. A promising approach for the sustainable production of natural products can be plant cell fermentation (PCF®). A thoroughly accomplished development process comprises the identification of a high producing cell line, optimization of growth and production conditions, the development of a robust and reliable production process and its scale-up. In order to address persistent, long lasting production, development of cryopreservation protocols and generation of working cell banks is another important requirement to be considered. So far the most prominent example using a PCF® process is the production of the anticancer compound paclitaxel. To demonstrate the power of plant suspension cultures here we present three case studies: 1) For more than 17 years Phyton produces paclitaxel at industrial scale i.e. up to 75,000 L in scale. With 60 g/kg dw this fully controlled process which is applied according to GMP results in outstanding high yields. 2) Thapsigargin is another anticancer compound which is currently isolated from seeds of Thapsia garganica. Thapsigargin is a powerful cytotoxin – a SERCA inhibitor – and the precursor for the derivative ADT, the key ingredient of the investigational prodrug Mipsagargin (G-202) which is in several clinical trials. Phyton successfully generated plant cell lines capable to express this compound. Here we present data about the screening for high producing cell lines. 3) The third case study covers ingenol-3-mebutate. This compound is found in the milky sap of the intact plants of the Euphorbiacae family at very low concentrations. Ingenol-3-mebutate is used in Picato® which is approved against actinic keratosis. Generation of cell lines expressing significant amounts of ingenol-3-mebutate is another example underlining the strength of plant cell culture. The authors gratefully acknowledge Inspyr Therapeutics for funding.Keywords: Ingenol-3-mebutate, plant cell culture, sustainability, thapsigargin
Procedia PDF Downloads 24482 Possibilities of Psychodiagnostics in the Context of Highly Challenging Situations in Military Leadership
Authors: Markéta Chmelíková, David Ullrich, Iva Burešová
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The paper maps the possibilities and limits of diagnosing selected personality and performance characteristics of military leadership and psychology students in the context of coping with challenging situations. Individuals vary greatly inter-individually in their ability to effectively manage extreme situations, yet existing diagnostic tools are often criticized mainly for their low predictive power. Nowadays, every modern army focuses primarily on the systematic minimization of potential risks, including the prediction of desirable forms of behavior and the performance of military commanders. The context of military leadership is well known for its life-threatening nature. Therefore, it is crucial to research stress load in the specific context of military leadership for the purpose of possible anticipation of human failure in managing extreme situations of military leadership. The aim of the submitted pilot study, using an experiment of 24 hours duration, is to verify the possibilities of a specific combination of psychodiagnostic to predict people who possess suitable equipment for coping with increased stress load. In our pilot study, we conducted an experiment of 24 hours duration with an experimental group (N=13) in the bomb shelter and a control group (N=11) in a classroom. Both groups were represented by military leadership students (N=11) and psychology students (N=13). Both groups were equalized in terms of study type and gender. Participants were administered the following test battery of personality characteristics: Big Five Inventory 2 (BFI-2), Short Dark Triad (SD-3), Emotion Regulation Questionnaire (ERQ), Fatigue Severity Scale (FSS), and Impulsive Behavior Scale (UPPS-P). This test battery was administered only once at the beginning of the experiment. Along with this, they were administered a test battery consisting of the Test of Attention (d2) and the Bourdon test four times overall with 6 hours ranges. To better simulate an extreme situation – we tried to induce sleep deprivation - participants were required to try not to fall asleep throughout the experiment. Despite the assumption that a stay in an underground bomb shelter will manifest in impaired cognitive performance, this expectation has been significantly confirmed in only one measurement, which can be interpreted as marginal in the context of multiple testing. This finding is a fundamental insight into the issue of stress management in extreme situations, which is crucial for effective military leadership. The results suggest that a 24-hour stay in a shelter, together with sleep deprivation, does not seem to simulate sufficient stress for an individual, which would be reflected in the level of cognitive performance. In the context of these findings, it would be interesting in future to extend the diagnostic battery with physiological indicators of stress, such as: heart rate, stress score, physical stress, mental stress ect.Keywords: bomb shelter, extreme situation, military leadership, psychodiagnostic
Procedia PDF Downloads 9081 Pentosan Polysulfate Sodium: A Potential Treatment to Improve Bone and Joint Manifestations of Mucopolysaccharidosis I
Authors: Drago Bratkovic, Curtis Gravance, David Ketteridge, Ravi Krishnan, Michael Imperiale
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The mucopolysaccharidoses (MPSs) are a group of lysosomal storage diseases that have a common defect in the catabolism of glycosaminoglycans (GAGs). MPS I is the most common of the MPS diseases. Manifestations of MPS I include coarsening of facial features, corneal clouding, developmental delay, short stature, skeletal manifestations, hearing loss, cardiac valve disease, hepatosplenomegaly, and umbilical and inguinal hernias. Treatments for MPS I restore or activate the missing or deficient enzyme in the case of enzyme replacement therapy (ERT) and haematopoietic stem cell transplantation (HSCT). Pentosan polysulfate sodium (PPS) is a potential treatment to improve bone and joint manifestations of MPS I. The mechanisms of action of PPS that are relevant to the treatment of MPS I are the ability to: (i) Reduce systemic and accumulated GAG, (ii) Reduce inflammatory effects via the inhibition of NF-kB, resulting in the reduction in pro-inflammatory mediators. (iii) Reduce the expression of the pain mediator nerve growth factor in osteocytes from degenerating joints. (iv) Inhibit the cartilage degrading enzymes related to joint dysfunction in MPS I. PPS is being evaluated as an adjunctive therapy to ERT and/or HSCT in an open-label, single-centre, phase 2 study. Patients are ≥ 5 years of age with a diagnosis of MPS I and previously received HSCT and/or ERT. Three white, female, patients with MPS I-Hurler, ages 14, 15, and 19 years, and one, white male patient aged 15 years are enrolled. All were diagnosed at ≤2 years of age. All patients received HSCT ≤ 6 months after diagnosis. Two of the patients were treated with ERT prior to HSCT, and 1 patient received ERT commencing 3 months prior to HSCT. Two patients received 0.75mg/kg and 2 patients received 1.5mg/kg of PPS. PPS was well tolerated at doses of 0.75 and 1.5 mg/kg to 47 weeks of continuous dosing. Of the 19 adverse events (AEs), 2 were related to PPS. One AE was moderate (pre-syncope) and 1 was mild (injection site bruising), experienced in the same patient. All AEs were reported as mild or moderate. There have been no SAEs. One subject experienced a COVID-19 infection and PPS was interrupted. The MPS I signature GAG fragments, sulfated disaccharide and UA-HNAc S, tended to decrease in 3 patients from baseline through Week 25. Week 25 GAG data are pending for the 4th patient. Overall, most biomarkers (inflammatory, cartilage degeneration, and bone turnover) evaluated in the 3 patients with 25-week assessments have indicated either no change or a reduction in levels compared to baseline. In 3 patients, there was a trend toward improvement in the 2MWT from baseline to Week 48 with > 100% increase in 1 patient (01-201). In the 3 patients that had Week 48 assessments, patients and proxies reported improvement in PGIC, including “worthwhile difference” (n=1), or “made all the difference” (n=2).Keywords: MPS I, pentosan polysulfate sodium, clinical study, 2MWT, QoL
Procedia PDF Downloads 11080 Transcription Skills and Written Composition in Chinese
Authors: Pui-sze Yeung, Connie Suk-han Ho, David Wai-ock Chan, Kevin Kien-hoa Chung
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Background: Recent findings have shown that transcription skills play a unique and significant role in Chinese word reading and spelling (i.e. word dictation), and written composition development. The interrelationships among component skills of transcription, word reading, word spelling, and written composition in Chinese have rarely been examined in the literature. Is the contribution of component skills of transcription to Chinese written composition mediated by word level skills (i.e., word reading and spelling)? Methods: The participants in the study were 249 Chinese children in Grade 1, Grade 3, and Grade 5 in Hong Kong. They were administered measures of general reasoning ability, orthographic knowledge, stroke sequence knowledge, word spelling, handwriting fluency, word reading, and Chinese narrative writing. Orthographic knowledge- orthographic knowledge was assessed by a task modeled after the lexical decision subtest of the Hong Kong Test of Specific Learning Difficulties in Reading and Writing (HKT-SpLD). Stroke sequence knowledge: The participants’ performance in producing legitimate stroke sequences was measured by a stroke sequence knowledge task. Handwriting fluency- Handwriting fluency was assessed by a task modeled after the Chinese Handwriting Speed Test. Word spelling: The stimuli of the word spelling task consist of fourteen two-character Chinese words. Word reading: The stimuli of the word reading task consist of 120 two-character Chinese words. Written composition: A narrative writing task was used to assess the participants’ text writing skills. Results: Analysis of covariance results showed that there were significant between-grade differences in the performance of word reading, word spelling, handwriting fluency, and written composition. Preliminary hierarchical multiple regression analysis results showed that orthographic knowledge, word spelling, and handwriting fluency were unique predictors of Chinese written composition even after controlling for age, IQ, and word reading. The interaction effects between grade and each of these three skills (orthographic knowledge, word spelling, and handwriting fluency) were not significant. Path analysis results showed that orthographic knowledge contributed to written composition both directly and indirectly through word spelling, while handwriting fluency contributed to written composition directly and indirectly through both word reading and spelling. Stroke sequence knowledge only contributed to written composition indirectly through word spelling. Conclusions: Preliminary hierarchical regression results were consistent with previous findings about the significant role of transcription skills in Chinese word reading, spelling and written composition development. The fact that orthographic knowledge contributed both directly and indirectly to written composition through word reading and spelling may reflect the impact of the script-sound-meaning convergence of Chinese characters on the composing process. The significant contribution of word spelling and handwriting fluency to Chinese written composition across elementary grades highlighted the difficulty in attaining automaticity of transcription skills in Chinese, which limits the working memory resources available for other composing processes.Keywords: orthographic knowledge, transcription skills, word reading, writing
Procedia PDF Downloads 42279 Functional Analysis of Variants Implicated in Hearing Loss in a Cohort from Argentina: From Molecular Diagnosis to Pre-Clinical Research
Authors: Paula I. Buonfiglio, Carlos David Bruque, Lucia Salatino, Vanesa Lotersztein, Sebastián Menazzi, Paola Plazas, Ana Belén Elgoyhen, Viviana Dalamón
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Hearing loss (HL) is the most prevalent sensorineural disorder affecting about 10% of the global population, with more than half due to genetic causes. About 1 in 500-1000 newborns present congenital HL. Most of the patients are non-syndromic with an autosomal recessive mode of inheritance. To date, more than 100 genes are related to HL. Therefore, the Whole-exome sequencing (WES) technique has become a cost-effective alternative approach for molecular diagnosis. Nevertheless, new challenges arise from the detection of novel variants, in particular missense changes, which can lead to a spectrum of genotype-to-phenotype correlations, which is not always straightforward. In this work, we aimed to identify the genetic causes of HL in isolated and familial cases by designing a multistep approach to analyze target genes related to hearing impairment. Moreover, we performed in silico and in vivo analyses in order to further study the effect of some of the novel variants identified in the hair cell function using the zebrafish model. A total of 650 patients were studied by Sanger Sequencing and Gap-PCR in GJB2 and GJB6 genes, respectively, diagnosing 15.5% of sporadic cases and 36% of familial ones. Overall, 50 different sequence variants were detected. Fifty of the undiagnosed patients with moderate HL were tested for deletions in STRC gene by Multiplex ligation-dependent probe amplification technique (MLPA), leading to 6% of diagnosis. After this initial screening, 50 families were selected to be analyzed by WES, achieving diagnosis in 44% of them. Half of the identified variants were novel. A missense variant in MYO6 gene detected in a family with postlingual HL was selected to be further analyzed. A protein modeling with AlphaFold2 software was performed, proving its pathogenic effect. In order to functionally validate this novel variant, a knockdown phenotype rescue assay in zebrafish was carried out. Injection of wild-type MYO6 mRNA in embryos rescued the phenotype, whereas using the mutant MYO6 mRNA (carrying c.2782C>A variant) had no effect. These results strongly suggest the deleterious effect of this variant on the mobility of stereocilia in zebrafish neuromasts, and hence on the auditory system. In the present work, we demonstrated that our algorithm is suitable for the sequential multigenic approach to HL in our cohort. These results highlight the importance of a combined strategy in order to identify candidate variants as well as the in silico and in vivo studies to analyze and prove their pathogenicity and accomplish a better understanding of the mechanisms underlying the physiopathology of the hearing impairment.Keywords: diagnosis, genetics, hearing loss, in silico analysis, in vivo analysis, WES, zebrafish
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