Search results for: brain drain
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 1257

Search results for: brain drain

657 Case of A Huge Retroperitoneal Abscess Spanning from the Diaphragm to the Pelvic Brim

Authors: Christopher Leung, Tony Kim, Rebecca Lendzion, Scott Mackenzie

Abstract:

Retroperitoneal abscesses are a rare but serious condition with often delayed diagnosis, non-specific symptoms, multiple causes and high morbidity/mortality. With the advent of more readily available cross-sectional imaging, retroperitoneal abscesses are treated earlier and better outcomes are achieved. Occasionally, a retroperitoneal abscess is present as a huge retroperitoneal abscess, as evident in this 53-year-old male. With a background of chronic renal disease and left partial nephrectomy, this gentleman presented with a one-month history of left flank pain without any other symptoms, including fevers or abdominal pain. CT abdomen and pelvis demonstrated a huge retroperitoneal abscess spanning from the diaphragm, abutting the spleen, down to the iliopsoas muscle and abutting the iliac vessels at the pelvic brim. This large retroperitoneal abscess required open drainage as well as drainage by interventional radiology. A long course of intravenous antibiotics and multiple drainages was required to drain the abscess. His blood culture and fluid culture grew Proteus species suggesting a urinary source, likely from his non-functioning kidney, which had a partial nephrectomy. Such a huge retroperitoneal abscess has rarely been described in the literature. The learning point here is that the basic principle of source control and antibiotics is paramount in treating retroperitoneal abscesses regardless of the size of the abscess.

Keywords: retroperitoneal abscess, retroperitoneal mass, sepsis, genitourinary infection

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656 Causes Analysis of Vacuum Consolidation Failure to Soft Foundation Filled by Newly Dredged Mud

Authors: Bao Shu-Feng, Lou Yan, Dong Zhi-Liang, Mo Hai-Hong, Chen Ping-Shan

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For soft foundation filled by newly dredged mud, after improved by Vacuum Preloading Technology (VPT), the soil strength was increased only a little, the effective improved depth was small, and the ground bearing capacity is still low. To analyze the causes in depth, it was conducted in laboratory of several comparative single well model experiments of VPT. It was concluded: (1) it mainly caused serious clogging problem and poor drainage performance in vertical drains of high content of fine soil particles and strong hydrophilic minerals in dredged mud, too fast loading rate at the early stage of vacuum preloading (namely rapidly reaching-80kPa) and too small characteristic opening size of the filter of the existed vertical drains; (2) it commonly reduced the drainage efficiency of drainage system, in turn weaken vacuum pressure in soils and soil improvement effect of the greater partial loss and friction loss of vacuum pressure caused by larger curvature of vertical drains and larger transfer resistance of vacuum pressure in horizontal drain.

Keywords: newly dredged mud, single well model experiments of vacuum preloading technology, poor drainage performance of vertical drains, poor soil improvement effect, causes analysis

Procedia PDF Downloads 258
655 A Case Report on Cognitive-Communication Intervention in Traumatic Brain Injury

Authors: Nikitha Francis, Anjana Hoode, Vinitha George, Jayashree S. Bhat

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The interaction between cognition and language, referred as cognitive-communication, is very intricate, involving several mental processes such as perception, memory, attention, lexical retrieval, decision making, motor planning, self-monitoring and knowledge. Cognitive-communication disorders are difficulties in communicative competencies that result from underlying cognitive impairments of attention, memory, organization, information processing, problem solving, and executive functions. Traumatic brain injury (TBI) is an acquired, non - progressive condition, resulting in distinct deficits of cognitive communication abilities such as naming, word-finding, self-monitoring, auditory recognition, attention, perception and memory. Cognitive-communication intervention in TBI is individualized, in order to enhance the person’s ability to process and interpret information for better functioning in their family and community life. The present case report illustrates the cognitive-communicative behaviors and the intervention outcomes of an adult with TBI, who was brought to the Department of Audiology and Speech Language Pathology, with cognitive and communicative disturbances, consequent to road traffic accident. On a detailed assessment, she showed naming deficits along with perseverations and had severe difficulty in recalling the details of the accident, her house address, places she had visited earlier, names of people known to her, as well as the activities she did each day, leading to severe breakdowns in her communicative abilities. She had difficulty in initiating, maintaining and following a conversation. She also lacked orientation to time and place. On administration of the Manipal Manual of Cognitive Linguistic Abilities (MMCLA), she exhibited poor performance on tasks related to visual and auditory perception, short term memory, working memory and executive functions. She attended 20 sessions of cognitive-communication intervention which followed a domain-general, adaptive training paradigm, with tasks relevant to everyday cognitive-communication skills. Compensatory strategies such as maintaining a dairy with reminders of her daily routine, names of people, date, time and place was also recommended. MMCLA was re-administered and her performance in the tasks showed significant improvements. Occurrence of perseverations and word retrieval difficulties reduced. She developed interests to initiate her day-to-day activities at home independently, as well as involve herself in conversations with her family members. Though she lacked awareness about her deficits, she actively involved herself in all the therapy activities. Rehabilitation of moderate to severe head injury patients can be done effectively through a holistic cognitive retraining with a focus on different cognitive-linguistic domains. Selection of goals and activities should have relevance to the functional needs of each individual with TBI, as highlighted in the present case report.

Keywords: cognitive-communication, executive functions, memory, traumatic brain injury

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654 Structural Correlates of Reduced Malicious Pleasure in Huntington's Disease

Authors: Sandra Baez, Mariana Pino, Mildred Berrio, Hernando Santamaria-Garcia, Lucas Sedeno, Adolfo Garcia, Sol Fittipaldi, Agustin Ibanez

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Schadenfreude refers to the perceiver’s experience of pleasure at another’s misfortune. This is a multidetermined emotion which can be evoked by hostile feelings and envy. The experience of Schadenfreude engages mechanisms implicated in diverse social cognitive processes. For instance, Schadenfreude involves heightened reward processing, accompanied by increased striatal engagement and it interacts with mentalizing and perspective-taking abilities. Patients with Huntington's disease (HD) exhibit reductions of Schadenfreude experience, suggesting a role of striatal degeneration in such an impairment. However, no study has directly assessed the relationship between regional brain atrophy in HD and reduced Schadenfreude. This study investigated whether gray matter (GM) atrophy in HD patients correlates with ratings of Schadenfreude. First, we compared the performance of 20 HD patients and 23 controls on an experimental task designed to trigger Schadenfreude and envy (another social emotion acting as a control condition). Second, we compared GM volume between groups. Third, we examined brain regions where atrophy might be associated with specific impairments in the patients. Results showed that while both groups showed similar ratings of envy, HD patients reported lower Schadenfreude. The latter pattern was related to atrophy in regions of the reward system (ventral striatum) and the mentalizing network (precuneus and superior parietal lobule). Our results shed light on the intertwining of reward and socioemotional processes in Schadenfreude, while offering novel evidence about their neural correlates. In addition, our results open the door to future studies investigating social emotion processing in other clinical populations characterized by striatal or mentalizing network impairments (e.g., Parkinson’s disease, schizophrenia, autism spectrum disorders).

Keywords: envy, Gray matter atrophy, Huntigton's disease, Schadenfreude, social emotions

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653 Joubert Syndrome and Related Disorders: A Single Center Experience

Authors: Ali Al Orf, Khawaja Bilal Waheed

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Background and objective: Joubert syndrome (JS) is a rare, autosomal-recessive condition. Early recognition is important for management and counseling. Magnetic resonance imaging (MRI) can help in diagnosis. Therefore, we sought to evaluate clinical presentation and MRI findings in Joubert syndrome and related disorders. Method: A retrospective review of genetically proven cases of Joubert syndromes and related disorders was reviewed for their clinical presentation, demographic information, and magnetic resonance imaging findings in a period of the last 10 years. Two radiologists documented magnetic resonance imaging (MRI) findings. The presence of hypoplasia of the cerebellar vermis with hypoplasia of the superior cerebellar peduncle resembling the “Molar Tooth Sign” in the mid-brain was documented. Genetic testing results were collected to label genes linked to the diagnoses. Results: Out of 12 genetically proven JS cases, most were females (9/12), and nearly all presented with hypotonia, ataxia, developmental delay, intellectual impairment, and speech disorders. 5/12 children presented at age of 1 or below. The molar tooth sign was seen in 10/12 cases. Two cases were associated with other brain findings. Most of the cases were found associated with consanguineous marriage Conclusion and discussion: The molar tooth sign is a frequent and reliable sign of JS and related disorders. Genes related to defective cilia result in malfunctioning in the retina, renal tubule, and neural cell migration, thus producing heterogeneous syndrome complexes known as “ciliopathies.” Other ciliopathies like Senior-Loken syndrome, Bardet Biedl syndrome, and isolated nephronophthisis must be considered as the differential diagnosis of JS. The main imaging findings are the partial or complete absence of the cerebellar vermis, hypoplastic cerebellar peduncles (giving MTS), and (bat-wing appearance) fourth ventricular deformity. LimitationsSingle-center, small sample size, and retrospective nature of the study were a few of the study limitations.

Keywords: Joubart syndrome, magnetic resonance imaging, molar tooth sign, hypotonia

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652 An Inquiry on Imaging of Soft Tissues in Micro-Computed Tomography

Authors: Matej Patzelt, Jana Mrzilkova, Jan Dudak, Frantisek Krejci, Jan Zemlicka, Zdenek Wurst, Petr Zach, Vladimir Musil

Abstract:

Introduction: Micro-CT is well used for examination of bone structures and teeth. On the other hand visualization of the soft tissues is still limited. The goal of our study was to elaborate methodology for soft tissue samples imaging in micro-CT. Methodology: We used organs of rats and mice. We either did a preparation of the organs and fixation in contrast solution or we did cannulation of blood vessels and their injection for imaging of the vascular system. First, we scanned native specimens, then we created corrosive specimens by resins. In the next step, we injected vascular system either by Aurovist contrast agent or by Exitron. In the next step, we focused on soft tissues contrast increase. We scanned samples fixated in Lugol solution, samples fixated in pure ethanol and in formaldehyde solution. All used methods were afterwards compared. Results: Native specimens did not provide sufficient contrast of the tissues in any of organs. Corrosive samples of the blood stream provided great contrast and details; on the other hand, it was necessary to destroy the organ. Further examined possibility was injection of the AuroVist contrast that leads to the great bloodstream contrast. Injection of Exitron contrast agent comparing to Aurovist did not provide such a great contrast. The soft tissues (kidney, heart, lungs, brain, and liver) were best visualized after fixation in ethanol. This type of fixation showed best results in all studied tissues. Lugol solution had great results in muscle tissue. Fixation by formaldehyde solution showed similar quality of contrast in the tissues like ethanol. Conclusion: Before imaging, we need to, first, determinate which structures of the soft tissues we want to visualize. In the case of the bloodstream, the best was AuroVist and corrosive specimens. Muscle tissue is best visualized by Lugol solution. In the case of the organs containing cavities, like kidneys or brain, the best way was ethanol fixation.

Keywords: experimental imaging, fixation, micro-CT, soft tissues

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651 Coronin 1C and miR-128A as Potential Diagnostic Biomarkers for Glioblastoma Multiform

Authors: Denis Mustafov, Emmanouil Karteris, Maria Braoudaki

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Glioblastoma multiform (GBM) is a heterogenous primary brain tumour that kills most affected patients. To the authors best knowledge, despite all research efforts there is no early diagnostic biomarker for GBM. MicroRNAs (miRNAs) are short non-coding RNA molecules which are deregulated in many cancers. The aim of this research was to determine miRNAs with a diagnostic impact and to potentially identify promising therapeutic targets for glioblastoma multiform. In silico analysis was performed to identify deregulated miRNAs with diagnostic relevance for glioblastoma. The expression profiles of the chosen miRNAs were then validated in vitro in the human glioblastoma cell lines A172 and U-87MG. Briefly, RNA extraction was carried out using the Trizol method, whilst miRNA extraction was performed using the mirVANA miRNA isolation kit. Quantitative Real-Time Polymerase Chain Reaction was performed to verify their expression. The presence of five target proteins within the A172 cell line was evaluated by Western blotting. The expression of the CORO1C protein within 32 GBM cases was examined via immunohistochemistry. The miRNAs identified in silico included miR-21-5p, miR-34a and miR-128a. These miRNAs were shown to target deregulated GBM genes, such as CDK6, E2F3, BMI1, JAG1, and CORO1C. miR-34a and miR-128a showed low expression profiles in comparison to a control miR-RNU-44 in both GBM cell lines suggesting tumour suppressor properties. Opposing, miR-21-5p demonstrated greater expression indicating that it could potentially function as an oncomiR. Western blotting revealed expression of all five proteins within the A172 cell line. In silico analysis also suggested that CORO1C is a target of miR-128a and miR-34a. Immunohistochemistry demonstrated that 75% of the GBM cases showed moderate to high expression of CORO1C protein. Greater understanding of the deregulated expression of miR-128a and the upregulation of CORO1C in GBM could potentially lead to the identification of a promising diagnostic biomarker signature for glioblastomas.

Keywords: non-coding RNAs, gene expression, brain tumours, immunohistochemistry

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650 Effect of Tai-Chi and Cyclic Meditation on Hemodynamic Responses of the Prefrontal Cortex: A Functional near Infrared Spectroscopy

Authors: Singh Deepeshwar, N. K. Manjunath, M. Avinash

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Meditation is a self-regulated conscious process associated with improved awareness, perception, attention and overall performance. Different traditional origin of meditation technique may have different effects on autonomic activity and brain functions. Based on this quest, the present study evaluated the effect of Tai-Chi Chuan (TCC, a Chines movement based meditation technique) and Cyclic Meditation (CM, an Indian traditional based stimulation and relaxation meditation technique) on the hemodynamic responses of the prefrontal cortex (PFC) and autonomic functions (such as R-R interval of heart rate variability and respiration). These two meditation practices were compared with simple walking. Employing 64 channel near infrared spectroscopy (NIRS), we measured hemoglobin concentration change (i.e., Oxyhemoglobin [ΔHbO], Deoxyhemoglobin [ΔHbR] and Total hemoglobin change [ΔTHC]) in the bilateral PFC before and after TCC, CM and Walking in young college students (n=25; average mean age ± SD; 23.4 ± 3.1 years). We observed the left PFC activity predominantly modulates sympathetic activity effects during the Tai-Chi whereas CM showed changes on right PFC with vagal dominance. However, the changes in oxyhemoglobin and total blood volume change after Tai-Chi was significant higher (p < 0.05, spam t-maps) on the left hemisphere, whereas after CM, there was a significant increase in oxyhemoglobin (p < 0.01) with a decrease in deoxyhemoglobin (p < 0.05) on right PFC. The normal walking showed decrease in Oxyhemoglobin with an increase in deoxyhemoglobin on left PFC. The autonomic functions result showed a significant increase in RR- interval (p < 0.05) along with significant reductions in HR (p < 0.05) in CM, whereas Tai-chi session showed significant increase in HR (p < 0.05) when compared to walking session. Within a group analysis showed a significant reduction in RR-I and significant increase in HR both in Tai-chi and walking sessions. The CM showed there were a significant improvement in the RR - interval of HRV (p < 0.01) with the reduction of heart rate and breath rate (p < 0.05). The result suggested that Tai-Chi and CM both have a positive effect on left and right prefrontal cortex and increase sympathovagal balance (alertful rest) in autonomic nervous system activity.

Keywords: brain, hemodynamic responses, yoga, meditation, Tai-Chi Chuan (TCC), walking, heart rate variability (HRV)

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649 Structural Assessment of Low-Rise Reinforced Concrete Frames under Tsunami Loads

Authors: Hussain Jiffry, Kypros Pilakoutas, Reyes Garcia Lopez

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This study examines the effect of tsunami loads on reinforced concrete (RC) frame buildings analytically. The impact of tsunami wave loads and waterborne objects are analyzed using a typical substandard full-scale two-story RC frame building tested as part of the EU-funded Ecoleader project. The building was subjected to shake table tests in bare condition and subsequently strengthened using Carbon Fiber Reinforced Polymers (CFRP) composites and retested. Numerical models of the building in both bare and CFRP-strengthened conditions are calibrated in DRAIN-3DX software to match the test results. To investigate the response of wave loads and impact forces, the numerical models are subjected to nonlinear dynamic analyses using force-time history input records. The analytical results are compared in terms of displacements at the floors and the 'impact point' of a boat. The results show that the roof displacement of the CFRP-strengthened building reduced by 63% when compared to the bare building. The results also indicate that strengthening only the mid-height of the impact column using CFRP is more efficient at reducing damage when compared to strengthening other parts of the column. Alternative solutions to mitigate damage due to tsunami loads are suggested.

Keywords: tsunami loads, hydrodynamic load, impact load, waterborne objects, RC buildings

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648 Going beyond the Traditional Offering in Modern Financial Services

Authors: Cam-Duc Au, Philippe Krahnhof, Lars Klingenberger

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German banks are experiencing harsh times due to rising costs and declining profits. On the one hand, acquisition costs for new customers are increasing because of the rise of innovative FinTechs, which entered the market with one specific goal: disrupting the whole financial services industry by occupying parts of the value chain. On the other hand, the COVID-19 pandemic, as well as an overall low level of interest rates, cause the traditional source of bank income to still drain. Consequently, traditional banks must rethink their strategies or their identity, so to speak, because they go beyond their traditional offering of products and services. Having said that, banks may create new sources of income to stabilize their economic situation and replenish profits. The given paper aims to research the opportunities of establishing an ecosystem model. In doing so, the paper contributes to the current literature debate and provide reference points for traditional banks to start. Firstly, a systematic literature review introduces a selection of research works the author regards as significant. In the following step, quantitative data from an online survey with bank clients are analysed by means of descriptive statistics to show the perspective of Germans with regards to an ecosystem offering. The final research findings indicate that the surveyed retail banking clients express interest in the new offer, whereas non-financial products and services are of lower interest than their financial pendants.

Keywords: banking, ecosystem, disruptive innovation, digital offering, open-banking-strategy, financial services industry

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647 The Analysis of Priority Flood Control Management Using Analysis Hierarchy Process

Authors: Pravira Rizki Suwarno, Fanny Aliza Savitri, Priseyola Ayunda Prima, Pipin Surahman, Mahelga Levina Amran, Khoirunisa Ulya Nur Utari, Nora Permatasari

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The Bogowonto River or commonly called the Bhagawanta River, is one of the rivers on Java Island. It is located in Central Java, Indonesia. Its watershed area is 35 km² with 57 km long. This river covers three regencies, namely Wonosobo Regency and Magelang Regency in the upstream and Purworejo Regency in the south and downstream. The Bogowonto River experiences channel narrowing and silting. It is caused by garbage along the river that comes from livestock and household waste. The narrowing channel and siltation cause a capacity reduction of the river to drain flood discharge. Comprehensive and sustainable actions are needed in dealing with current and future floods. Based on these current conditions, a priority scale is required. Therefore, this study aims to determine the priority scale of flood management in Purworejo Regency using the Analytical Hierarchy Process (AHP) method. This method will determine the appropriate actions based on the rating. In addition, there will be field observations through distributing questionnaires to several parties, including the stakeholders and the community. The results of this study will be in 2 (two) forms of actions, both structurally covering water structures and non-structural, including social, environmental, and law enforcement.

Keywords: analytical hierarchy process, bogowonto, flood control, management

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646 Altered States of Consciousness in Narrative Cinema: Subjective Film Sound

Authors: Mladen Milicevic

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In this paper, subjective film sound will be addressed as it gets represented in narrative cinema. First, 'meta-diegetic' sound will be briefly explained followed by transition to “oneiric” sound. The representation of oneiric sound refers to a situation where film characters are experiencing some sort of an altered state of consciousness. Looking at an antlered state of consciousness in terms of human brain processes will point out to the cinematic ways of expression, which 'mimic' those processes. Using several examples for different films will illustrate these points.

Keywords: oneiric, ASC, film, sound

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645 Asymmetrically Contacted Tellurium Short-Wave Infrared Photodetector with Low Dark Current and High Sensitivity at Room Temperature

Authors: Huang Haoxin

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Large dark current at room temperature has long been the major bottleneck that impedes the development of high-performance infrared photodetectors towards miniaturization and integration. Although infrared photodetectors based on layered 2D narrow bandgap semiconductors have shown admirable advantages compared with those based on conventional compounds, which typically suffer from expensive cryogenic operations, it is still urgent to develop a simple but effective strategy to further reduce the dark current. Herein, a tellurium (Te) based infrared photodetector is reported with a specifically designed asymmetric electrical contact area. The deliberately introduced asymmetric electrical contact raises the electric field intensity difference in the Te channel near the drain and the source electrodes, resulting in spontaneous asymmetric carrier diffusion under global infrared light illumination under zero bias. Specifically, the Te-based photodetector presents promising detector performance at room temperature, including a low dark current of≈1 nA, an ultrahigh photocurrent/dark current ratio of 1.57×10⁴, a high specific detectivity (D*) of 3.24×10⁹ Jones, and relatively fast response speed of ≈720 μs at zero bias. The results prove that the simple design of asymmetric electrical contact areas can provide a promising solution to high-performance 2D semiconductor-based infrared photodetectors working at room temperature.

Keywords: asymmetrical contact, tellurium, dark current, infrared photodetector, sensitivity

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644 Load-Enabled Deployment and Sensing Range Optimization for Lifetime Enhancement of WSNs

Authors: Krishan P. Sharma, T. P. Sharma

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Wireless sensor nodes are resource constrained battery powered devices usually deployed in hostile and ill-disposed areas to cooperatively monitor physical or environmental conditions. Due to their limited power supply, the major challenge for researchers is to utilize their battery power for enhancing the lifetime of whole network. Communication and sensing are two major sources of energy consumption in sensor networks. In this paper, we propose a deployment strategy for enhancing the average lifetime of a sensor network by effectively utilizing communication and sensing energy to provide full coverage. The proposed scheme is based on the fact that due to heavy relaying load, sensor nodes near to the sink drain energy at much faster rate than other nodes in the network and consequently die much earlier. To cover this imbalance, proposed scheme finds optimal communication and sensing ranges according to effective load at each node and uses a non-uniform deployment strategy where there is a comparatively high density of nodes near to the sink. Probable relaying load factor at particular node is calculated and accordingly optimal communication distance and sensing range for each sensor node is adjusted. Thus, sensor nodes are placed at locations that optimize energy during network operation. Formal mathematical analysis for calculating optimized locations is reported in present work.

Keywords: load factor, network lifetime, non-uniform deployment, sensing range

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643 Hard Sludge Formation and Consolidation in Pressurized Water Reactor Steam Generators: An Experimental Study

Authors: R. Fernandez-Saavedra, M. B. Gomez-Mancebo, D. Gomez-Briceno

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The gradual corrosion of PWR (Pressurized Water Reactor) feedwater, condensate and drain systems results in the inevitable liberation of corrosion products, principally metallic oxides, to the secondary circuit. In addition, other contaminants and impurities are introduced into the makeup water, auxiliary feedwater and by condenser leaks. All these compounds circulating in the secondary flow can eventually be transported to steam generators and be transformed into deposits on their surfaces. Deposits that accumulate on the tube sheet are known as sludge piles and when they consolidate and harden become into hard sludge. Hard sludge is especially detrimental because it favors tube deformation or denting at the top of tube sheet and further stress corrosion cracking (SCC). These failures affect the efficiency of nuclear power plants. In a recent work, a model for the formation and consolidation of hard sludge has been formulated, highlighting the influence of aluminum and silicon compounds in the initial formation of hard sludge. In this work, an experimental study has been performed in order to get a deeper understanding of the behavior of Al and Si species in hard sludge formation and consolidation. For this purpose, the key components of hard sludge (magnetite, aluminum and/or silicon sources) have been isothermally autoclaved in representative secondary circuit conditions during one week, and the resulting products have been chemically and structurally characterized by XRF and XRD techniques, respectively.

Keywords: consolidation, hard sludge, secondary circuit, steam generator

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642 Effect of Papaverine on Developmental Neurotoxicity: Neurosphere as in vitro Model

Authors: Mohammed Y. Elsherbeny, Mohamed Salama, Ahmed Lotfy, Hossam Fareed, Nora Mohammed

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Background: Developmental neurotoxicity (DNT) entails the toxic effects imparted by various chemicals on brain during the early childhood when human brains are vulnerable during this period. DNT study in vivo cannot determine the effect of the neurotoxins, as it is not applicable, so using the neurosphere cells of lab animals as an alternative is applicable and time saving. Methods: Cell culture: Rat neural progenitor cells were isolated from rat embryos’ brain. The cortices were aseptically dissected out and the tissues were triturated. The dispersed tissues were allowed to settle. The supernatant was then transferred to a fresh tube and centrifuged. The pellet was placed in Hank’s balanced salt solution and cultured as free-floating neurospheres in proliferation medium. Differentiation was initiated by growth factor withdrawal in differentiation medium and plating onto a poly-d-lysine/ laminin matrix. Chemical Exposure: Neurospheres were treated for 2 weeks with papaverine in proliferation medium. Proliferation analyses: Spheres were cultured. After 0, 4, 5, 11 and 14 days, sphere size was determined by software analyses (CellProfiler, version 2.1; Broad Institute). Diameter of each neurosphere was measured and exported to excel file further to statistical analysis. Viability test: Trypsin-EDTA solution was added to neurospheres to dissociate neurospheres into single cells suspension, then viability evaluated by the Trypan Blue exclusion test. Result: As regards proliferation analysis and percentage of viable cells of papaverin treated groups: There was no significant change in cells proliferation compared to control at 0, 4, 5, 11 and 14 days with concentrations 1, 5 and 10 µM of papaverine, but there is a significant change in cell viability compared to control after 1 week and 2 weeks with the same concentrations of papaverine. Conclusion: Papaverine has toxic effect on viability of neural cell, not on their proliferation, so it may produce focal neural lesions not growth morphological changes.

Keywords: developmental neurotoxicity, neurotoxin, papaverine, neuroshperes

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641 Connectomic Correlates of Cerebral Microhemorrhages in Mild Traumatic Brain Injury Victims with Neural and Cognitive Deficits

Authors: Kenneth A. Rostowsky, Alexander S. Maher, Nahian F. Chowdhury, Andrei Irimia

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The clinical significance of cerebral microbleeds (CMBs) due to mild traumatic brain injury (mTBI) remains unclear. Here we use magnetic resonance imaging (MRI), diffusion tensor imaging (DTI) and connectomic analysis to investigate the statistical association between mTBI-related CMBs, post-TBI changes to the human connectome and neurological/cognitive deficits. This study was undertaken in agreement with US federal law (45 CFR 46) and was approved by the Institutional Review Board (IRB) of the University of Southern California (USC). Two groups, one consisting of 26 (13 females) mTBI victims and another comprising 26 (13 females) healthy control (HC) volunteers were recruited through IRB-approved procedures. The acute Glasgow Coma Scale (GCS) score was available for each mTBI victim (mean µ = 13.2; standard deviation σ = 0.4). Each HC volunteer was assigned a GCS of 15 to indicate the absence of head trauma at the time of enrollment in our study. Volunteers in the HC and mTBI groups were matched according to their sex and age (HC: µ = 67.2 years, σ = 5.62 years; mTBI: µ = 66.8 years, σ = 5.93 years). MRI [including T1- and T2-weighted volumes, gradient recalled echo (GRE)/susceptibility weighted imaging (SWI)] and gradient echo (GE) DWI volumes were acquired using the same MRI scanner type (Trio TIM, Siemens Corp.). Skull-stripping and eddy current correction were implemented. DWI volumes were processed in TrackVis (http://trackvis.org) and 3D Slicer (http://www.slicer.org). Tensors were fit to DWI data to perform DTI, and tractography streamlines were then reconstructed using deterministic tractography. A voxel classifier was used to identify image features as CMB candidates using Microbleed Anatomic Rating Scale (MARS) guidelines. For each peri-lesional DTI streamline bundle, the null hypothesis was formulated as the statement that there was no neurological or cognitive deficit associated with between-scan differences in the mean FA of DTI streamlines within each bundle. The statistical significance of each hypothesis test was calculated at the α = 0.05 level, subject to the family-wise error rate (FWER) correction for multiple comparisons. Results: In HC volunteers, the along-track analysis failed to identify statistically significant differences in the mean FA of DTI streamline bundles. In the mTBI group, significant differences in the mean FA of peri-lesional streamline bundles were found in 21 out of 26 volunteers. In those volunteers where significant differences had been found, these differences were associated with an average of ~47% of all identified CMBs (σ = 21%). In 12 out of the 21 volunteers exhibiting significant FA changes, cognitive functions (memory acquisition and retrieval, top-down control of attention, planning, judgment, cognitive aspects of decision-making) were found to have deteriorated over the six months following injury (r = -0.32, p < 0.001). Our preliminary results suggest that acute post-TBI CMBs may be associated with cognitive decline in some mTBI patients. Future research should attempt to identify mTBI patients at high risk for cognitive sequelae.

Keywords: traumatic brain injury, magnetic resonance imaging, diffusion tensor imaging, connectomics

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640 Assessment of Potentially Harmful Elements in Floodplain Soils and Stream Sediments in Ile-Ife Area, South-Western Nigeria: Using Geographic Information System and Multi-Variances Approaches

Authors: I. T. Asowata, A. S. Akinwumiju

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The enrichment of potentially harmful elements (PHEs) in stream sediments (SS) and floodplain soils (FS) poses great environmental hazards to water bodies and other parts of the ecosystem. The aim of this research was to assess the distribution pattern of selected PHEs (Cu, Pb, Zn, Co, Mn, As, Cd, V, Cr, Ni, Th, Sr, and La) in SS of selected rivers that drain Ile-Ife area and their adjacent FS, to ascertain the pollution status of these elements in the study area. 60 samples (40 SS and 20 FS) were purposely collected for this study; the samples were air-dried at room temperature, disaggregated, sieved with > 63 µm and digested with modified aqua reqia (1:1:1 HCl:HNO₃:H₂O) and were analysed with ultra-trace inductively coupled plasma mass spectrometry method (ICP-ES). The geochemical results showed decreasing trend of average contents of PHEs studied Mn > Zn > V > Cr > Pb > La > Sr > Cu > Ni > Co > Th > As > Cd for both SS and FS. Floodplain topsoil in ppm, Cu range from 10.0-180.0; mean, 71.1, Pb, 17.1-255.0; 93.5 and Zn, 83.0-3122.2; 826.0. Also, floodplain sub-soils, Cu range from 30.0-203.1; mean of 76.6, Pb, 16.0-214.0; 77.9 and Zn, 59.1-2351.0; 622.3. Similarly, SS results for Cu, 22.1-257.0; 70.3, Pb, 15.0-172.0; 67.3 and Zn, 65.0-1285.0; 357.8, among other PHEs, suggesting significant level of PHEs enrichment in the studied geo media. Elemental association showed positive and/or negative correlation among the PHEs and also showed different sources of metal enrichment to be largely anthropogenic with some geogenic. Geoaccumulation and metal ratio indexes indicated that FS and SS studied have received significant PHEs of between moderately to strongly polluted, which implies significant environmental implications in the study area.

Keywords: aqua regia, enrichment, GIS, Ile-Ife, potentially harmful elements

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639 CD97 and Its Role in Glioblastoma Stem Cell Self-Renewal

Authors: Niklas Ravn-Boess, Nainita Bhowmick, Takamitsu Hattori, Shohei Koide, Christopher Park, Dimitris Placantonakis

Abstract:

Background: Glioblastoma (GBM) is the most common and deadly primary brain malignancy in adults. Tumor propagation, brain invasion, and resistance to therapy critically depend on GBM stem-like cells (GSCs); however, the mechanisms that regulate GSC self-renewal are incompletely understood. Given the aggressiveness and poor prognosis of GBM, it is imperative to find biomarkers that could also translate into novel drug targets. Along these lines, we have identified a cell surface antigen, CD97 (ADGRE5), an adhesion G protein-coupled receptor (GPCR), that is expressed on GBM cells but is absent from non-neoplastic brain tissue. CD97 has been shown to promote invasiveness, angiogenesis, and migration in several human cancers, but its frequency of expression and functional role in regulating GBM growth and survival, and its potential as a therapeutic target has not been investigated. Design: We assessed CD97 mRNA and protein expression in patient derived GBM samples and cell lines using publicly available RNA-sequencing datasets and flow cytometry, respectively. To assess CD97 function, we generated shRNA lentiviral constructs that target a sequence in the CD97 extracellular domain (ECD). A scrambled shRNA (scr) with no predicted targets in the genome was used as a control. We evaluated CD97 shRNA lentivirally transduced GBM cells for Ki67, Annexin V, and DAPI. We also tested CD97 KD cells for their ability to self-renew using clonogenic tumorsphere formation assays. Further, we utilized synthetic Abs (sAbs) generated against the ECD of CD97 to test for potential antitumor effects using patient-derived GBM cell lines. Results: CD97 mRNA expression was expressed at high levels in all GBM samples available in the TCGA cohort. We found high levels of surface CD97 protein expression in 6/6 patient-derived GBM cell cultures, but not human neural stem cells. Flow cytometry confirmed downregulation of CD97 in CD97 shRNA lentivirally transduced cells. CD97 KD induced a significant reduction in cell growth in 3 independent GBM cell lines representing mesenchymal and proneural subtypes, which was accompanied by reduced (~20%) Ki67 staining and increased (~30%) apoptosis. Incubation of GBM cells with sAbs (20 ug/ ml) against the ECD of CD97 for 3 days induced GSC differentiation, as determined by the expression of GFAP and Tubulin. Using three unique GBM patient derived cultures, we found that CD97 KD attenuated the ability of GBM cells to initiate sphere formation by over 300 fold, consistent with an impairment in GSC self-renewal. Conclusion: Loss of CD97 expression in patient-derived GBM cells markedly decreases proliferation, induces cell death, and reduces tumorsphere formation. sAbs against the ECD of CD97 reduce tumorsphere formation, recapitulating the phenotype of CD97 KD, suggesting that sAbs that inhibit CD97 function exhibit anti-tumor activity. Collectively, these findings indicate that CD97 is necessary for the proliferation and survival of human GBM cells and identify CD97 as a promising therapeutically targetable vulnerability in GBM.

Keywords: adhesion GPCR, CD97, GBM stem cell, glioblastoma

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

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

Abstract:

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

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

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637 Comparative Efficacy of Angiotensin Converting Enzymes Inhibitors and Angiotensin Receptor Blockers in Patients with Heart Failure in Tanzania: A Prospective Cohort Study

Authors: Mark P. Mayala, Henry Mayala, Khuzeima Khanbhai

Abstract:

Background: Heart failure has been a rising concern in Tanzania. New drugs have been introduced, including the group of drugs called Angiotensin receptor Neprilysin Inhibitor (ARNI), but due to their high cost, angiotensin-converting enzymes inhibitors (ACEIs) and Angiotensin receptor blockers (ARBs) have been mostly used in Tanzania. However, according to our knowledge, the efficacy comparison of the two groups is yet to be studied in Tanzania. The aim of this study was to compare the efficacy of ACEIs and ARBs among patients with heart failure. Methodology: This was a hospital-based prospective cohort study done at Jakaya Kikwete Cardiac Institution (JKCI), Tanzania, from June to December 2020. Consecutive enrollment was done until fulfilling the inclusion criteria. Clinical details were measured at baseline. We assessed the relationship between ARBs and ACEIs users with N-terminal pro-brain natriuretic peptide (NT pro-BNP) levels at admission and at 1-month follow-up using a chi-square test. A Kaplan-Meier curve was used to estimate the survival time of the two groups. Results: 155 HF patients were enrolled, with a mean age of 48 years, whereby 52.3% were male, and their mean left ventricular ejection fraction (LVEF) was 37.3%. 52 (33.5%) heart failure patients were on ACEIs, 57 (36.8%) on ARBs, and 46 (29.7%) were neither using ACEIs nor ARBs. At least half of the patients did not receive a guideline-directed medical therapy (GDMT), with only 82 (52.9%) receiving a GDMT. A drop in NT pro-BNP levels was observed during admission and at 1-month follow-up on both groups, from 6389.2 pg/ml to 4000.1 pg/ml for ARB users and 5877.7 pg/ml to 1328.2 pg/ml for the ACEIs users. There was no statistical difference between the two groups when estimated by the Kaplan-Meier curve, though more deaths were observed in those who were neither on ACEIs nor ARBs, with a calculated P value of 0.01. Conclusion: This study demonstrates that ACEIs have more efficacy and overall better clinical outcome than ARBs, but this should be taken under the patient-based case, considering the side effects of ACEIs and patients’ adherence.

Keywords: angiotensin converting enzymes inhibitors, angiotensin receptor blockers, guideline direct medical therapy, N-terminal pro-brain natriuretic peptide

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636 Multi-omics Integrative Analysis with Genome-Scale Metabolic Model Simulation Reveals Reaction Essentiality data in Human Astrocytes Under the Lipotoxic Effect of Palmitic Acid

Authors: Janneth Gonzalez, Andres Pinzon Velasco, Maria Angarita, Nicolas Mendoza

Abstract:

Astrocytes play an important role in various processes in the brain, including pathological conditions such as neurodegenerative diseases. Recent studies have shown that the increase in saturated fatty acids such as palmitic acid (PA) triggers pro-inflammatory pathways in the brain. The use of synthetic neurosteroids such as tibolone has demonstrated neuro-protective mechanisms. However, there are few studies on the neuro-protective mechanisms of tibolone, especially at the systemic (omic) level. In this study, we performed the integration of multi-omic data (transcriptome and proteome) into a human astrocyte genomic scale metabolic model to study the astrocytic response during palmitate treatment. We evaluated metabolic fluxes in three scenarios (healthy, induced inflammation by PA, and tibolone treatment under PA inflammation). We also use control theory to identify those reactions that control the astrocytic system. Our results suggest that PA generates a modulation of central and secondary metabolism, showing a change in energy source use through inhibition of folate cycle and fatty acid β-oxidation and upregulation of ketone bodies formation.We found 25 metabolic switches under PA-mediated cellular regulation, 9 of which were critical only in the inflammatory scenario but not in the protective tibolone one. Within these reactions, inhibitory, total, and directional coupling profiles were key findings, playing a fundamental role in the (de)regulation in metabolic pathways that increase neurotoxicity and represent potential treatment targets. Finally, this study framework facilitates the understanding of metabolic regulation strategies, andit can be used for in silico exploring the mechanisms of astrocytic cell regulation, directing a more complex future experimental work in neurodegenerative diseases.

Keywords: astrocytes, data integration, palmitic acid, computational model, multi-omics, control theory

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635 The Functional Magnetic Resonance Imaging and the Consumer Behaviour: Reviewing Recent Research

Authors: Mikel Alonso López

Abstract:

In the first decade of the twenty-first century, advanced imaging techniques began to be applied for neuroscience research. The Functional Magnetic Resonance Imaging (fMRI) is one of the most important and most used research techniques for the investigation of emotions, because of its ease to observe the brain areas that oxygenate when performing certain tasks. In this research, we make a review about the main research carried out on the influence of the emotions in the decision-making process that is exposed by using the fMRI.

Keywords: decision making, emotions, fMRI, consumer behaviour

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634 Application of Watershed Modeling System for Urbanization Management in Tabuk Area, Saudi Arabia

Authors: Abd-Alrahman Embaby, Ayman Abu Halawa, Medhat Ramadan

Abstract:

The infiltrated water into the subsurface activates expansive soil in localized manner, leading to the differential heaving and destructive of the construction. The Watershed Modeling System (WMS) and Hydrologic Engineering Center (HEC-1) are used to delineate and identify the drainage system and basin morphometry in Tabuk area, where flash floods and accumulation of water may take place. Eight drainage basins effect on Tabuk city. Three of them are expected to be high. The flash floods and surface runoff behavior in these basins are important for any protection projects. It was found that the risky areas that contain Tabuk shale could be expanded when exposed to flash floods and/or surface runoff. The resident neighborhoods in the middle of Tabuk city and affected by surface runoff of the tributaries of the basin of Wadi Abu Nishayfah, Na'am and Atanah outlet, represent high-risk zones. These high-risk neighborhoods are Al Qadsiyah, Al Maseif, Arrwdah, Al Nakhil and Al Rajhi. It can be avoided new constructions on these districts. The low or very low-risk zones include the western and the eastern districts. The western side of the city is lying in the upstream of the small basin. It is suitable for a future urban extension. The direction of surface runoff flow or storm water drain discharge should be away from Tabuk city. The quicker the water can flow out, the better it is.

Keywords: digital elevation model (DEM), flash floods, Saudi Arabia, Tabuk City, watershed modeling system (WMS)

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633 Concepts of Instrumentation Scheme for Thought Transfer

Authors: Rai Sachindra Prasad

Abstract:

Thought is physical force. This has been well recognized but hardly translated visually or otherwise in the sense of its transfer from one individual to another. In the present world of chaos and disorder with yawning gaps between right and wrong thinking individuals, if it is possible to transfer the right thoughts to replace the wrong ones it would indeed be a great achievement in the present situation of the world which is torn with violence with dangerous thoughts of individuals. Moreover, such a possibility would completely remove the barrier of language between two persons, which at times proves to be a great obstacle in realizing a desired purpose. If a proper instrumentation scheme containing appropriate transducers and electronics is designed and implemented to realize this thought ransfer phenomenon, this would prove to be extremely useful when properly used. Considering the advancements already made in recording the nerve impulses in the brain, which are electrical events of very short durations that move along the axon, it is conceivable that this may be used to good effect in implementing the scheme. In such a proposition one shoud consider the roles played by pineal body, pituitary gland and ‘association’ areas. Pioneer students of brain have thought that associations or connections between sensory input and motor output were made in these areas. It is currently believed that rather than being regions of simple sensory-motor connections, the association areas process and integrate sensory information relayed to them from the primary sensory areas of the cortex and from the thalamus, after the information has been processed, it may be sent to motor areas to be acted upon. Again, even though the role played by pineal body is not known fully to neurologists its interconnection with pituitary gland is a matter of great significance to the ‘Rishis’ and; Seers’ s described in Vedas and Puranas- the ancient Holy books of Hindus. If the pineal body is activated through meditation it would control the pituitary gland thereby the individual’s thoughts and acts. Thus, if thoughts can be picked up by special transducers, these can be connected to suitable electronics circuitry to amplify the signals. These signals in the form of electromagnetic waves can then be transmitted using modems for long distance transmission and eventually received by or passed on to a subject of interest through another set of electronics circuit and devices.

Keywords: modems, pituitary gland, pineal body, thought transfer

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632 Rapid and Sensitive Detection: Biosensors as an Innovative Analytical Tools

Authors: Sylwia Baluta, Joanna Cabaj, Karol Malecha

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The evolution of biosensors was driven by the need for faster and more versatile analytical methods for application in important areas including clinical, diagnostics, food analysis or environmental monitoring, with minimum sample pretreatment. Rapid and sensitive neurotransmitters detection is extremely important in modern medicine. These compounds mainly occur in the brain and central nervous system of mammals. Any changes in the neurotransmitters concentration may lead to many diseases, such as Parkinson’s or schizophrenia. Classical techniques of chemical analysis, despite many advantages, do not permit to obtain immediate results or automatization of measurements.

Keywords: adrenaline, biosensor, dopamine, laccase, tyrosinase

Procedia PDF Downloads 123
631 Subjective Evaluation of Mathematical Morphology Edge Detection on Computed Tomography (CT) Images

Authors: Emhimed Saffor

Abstract:

In this paper, the problem of edge detection in digital images is considered. Three methods of edge detection based on mathematical morphology algorithm were applied on two sets (Brain and Chest) CT images. 3x3 filter for first method, 5x5 filter for second method and 7x7 filter for third method under MATLAB programming environment. The results of the above-mentioned methods are subjectively evaluated. The results show these methods are more efficient and satiable for medical images, and they can be used for different other applications.

Keywords: CT images, Matlab, medical images, edge detection

Procedia PDF Downloads 308
630 Association between Attention Deficit Hyperactivity Disorder Medication, Cannabis, and Nicotine Use, Mental Distress, and Other Psychoactive Substances

Authors: Nicole Scott, Emily Dwyer, Cara Patrissy, Samantha Bonventre, Lina Begdache

Abstract:

Across North America, the use and abuse of Attention Deficit Hyperactivity Disorder (ADHD) medication, cannabis, nicotine, and other psychoactive substances across college campuses have become an increasingly prevalent problem. Students frequently use these substances to aid their studying or deal with their mental health issues. However, it is still unknown what psychoactive substances are likely to be abused when college students illicitly use ADHD medication. In addition, it is not clear which psychoactive substance is associated with mental distress. Thus, the purpose of this study is to fill these gaps by assessing the use of different psychoactive substances when illicit ADHD medication is used; and how this association relates to mental stress. A total of 702 undergraduate students from different college campuses in the U.S. completed an anonymous survey distributed online. Data were self-reported on demographics, the use of ADHD medications, cannabis, nicotine, other psychoactive drugs, and mental distress, and feelings and opinions on the use of illicit study drugs were all included in the survey. Mental distress was assessed using the Kessler Psychological Distress 6 Scale. Data were analyzed in SPSS, Version 25.0, using Pearson’s Correlation Coefficient. Our results show that use of ADHD medication, cannabis use (non-frequent and very frequent), and nicotine use (non-frequent and very frequent), there were both statistically significant positive and negative correlations to specific psychoactive substances and their corresponding frequencies. Along the same lines, ADHD medication, cannabis use (non-frequent and very frequent), and nicotine use (non-frequent and very frequent) had statistically significant positive and negative correlations to specific mental distress experiences. As these findings are combined, a vicious loop can initiate a cycle where individuals who abuse psychoactive substances may or may not be inclined to use other psychoactive substances. This may later inhibit brain functions in those main areas of the brain stem, amygdala, and prefrontal cortex where this vicious cycle may or may not impact their mental distress. Addressing the impact of study drug abuse and its potential to be associated with further substance abuse may provide an educational framework and support proactive approaches to promote awareness among college students.

Keywords: stimulant, depressant, nicotine, ADHD medication, psychoactive substances, mental health, illicit, ecstasy, adrenochrome

Procedia PDF Downloads 46
629 Multi-Omics Integrative Analysis Coupled to Control Theory and Computational Simulation of a Genome-Scale Metabolic Model Reveal Controlling Biological Switches in Human Astrocytes under Palmitic Acid-Induced Lipotoxicity

Authors: Janneth Gonzalez, Andrés Pinzon Velasco, Maria Angarita

Abstract:

Astrocytes play an important role in various processes in the brain, including pathological conditions such as neurodegenerative diseases. Recent studies have shown that the increase in saturated fatty acids such as palmitic acid (PA) triggers pro-inflammatorypathways in the brain. The use of synthetic neurosteroids such as tibolone has demonstrated neuro-protective mechanisms. However, broad studies with a systemic point of view on the neurodegenerative role of PA and the neuro-protective mechanisms of tibolone are lacking. In this study, we performed the integration of multi-omic data (transcriptome and proteome) into a human astrocyte genomic scale metabolic model to study the astrocytic response during palmitate treatment. We evaluated metabolic fluxes in three scenarios (healthy, induced inflammation by PA, and tibolone treatment under PA inflammation). We also applied a control theory approach to identify those reactions that exert more control in the astrocytic system. Our results suggest that PA generates a modulation of central and secondary metabolism, showing a switch in energy source use through inhibition of folate cycle and fatty acid β‐oxidation and upregulation of ketone bodies formation. We found 25 metabolic switches under PA‐mediated cellular regulation, 9 of which were critical only in the inflammatory scenario but not in the protective tibolone one. Within these reactions, inhibitory, total, and directional coupling profiles were key findings, playing a fundamental role in the (de)regulation of metabolic pathways that may increase neurotoxicity and represent potential treatment targets. Finally, the overall framework of our approach facilitates the understanding of complex metabolic regulation, and it can be used for in silico exploration of the mechanisms of astrocytic cell regulation, directing a more complex future experimental work in neurodegenerative diseases.

Keywords: astrocytes, data integration, palmitic acid, computational model, multi-omics

Procedia PDF Downloads 84
628 Exploring the Neural Mechanisms of Communication and Cooperation in Children and Adults

Authors: Sara Mosteller, Larissa K. Samuelson, Sobanawartiny Wijeakumar, John P. Spencer

Abstract:

This study was designed to examine how humans are able to teach and learn semantic information as well as cooperate in order to jointly achieve sophisticated goals. Specifically, we are measuring individual differences in how these abilities develop from foundational building blocks in early childhood. The current study adopts a paradigm for novel noun learning developed by Samuelson, Smith, Perry, and Spencer (2011) to a hyperscanning paradigm [Cui, Bryant and Reiss, 2012]. This project measures coordinated brain activity between a parent and child using simultaneous functional near infrared spectroscopy (fNIRS) in pairs of 2.5, 3.5 and 4.5-year-old children and their parents. We are also separately testing pairs of adult friends. Children and parents, or adult friends, are seated across from one another at a table. The parent (in the developmental study) then teaches their child the names of novel toys. An experimenter then tests the child by presenting the objects in pairs and asking the child to retrieve one object by name. Children are asked to choose from both pairs of familiar objects and pairs of novel objects. In order to explore individual differences in cooperation with the same participants, each dyad plays a cooperative game of Jenga, in which their joint score is based on how many blocks they can remove from the tower as a team. A preliminary analysis of the noun-learning task showed that, when presented with 6 word-object mappings, children learned an average of 3 new words (50%) and that the number of objects learned by each child ranged from 2-4. Adults initially learned all of the new words but were variable in their later retention of the mappings, which ranged from 50-100%. We are currently examining differences in cooperative behavior during the Jenga playing game, including time spent discussing each move before it is made. Ongoing analyses are examining the social dynamics that might underlie the differences between words that were successfully learned and unlearned words for each dyad, as well as the developmental differences observed in the study. Additionally, the Jenga game is being used to better understand individual and developmental differences in social coordination during a cooperative task. At a behavioral level, the analysis maps periods of joint visual attention between participants during the word learning and the Jenga game, using head-mounted eye trackers to assess each participant’s first-person viewpoint during the session. We are also analyzing the coherence in brain activity between participants during novel word-learning and Jenga playing. The first hypothesis is that visual joint attention during the session will be positively correlated with both the number of words learned and with the number of blocks moved during Jenga before the tower falls. The next hypothesis is that successful communication of new words and success in the game will each be positively correlated with synchronized brain activity between the parent and child/the adult friends in cortical regions underlying social cognition, semantic processing, and visual processing. This study probes both the neural and behavioral mechanisms of learning and cooperation in a naturalistic, interactive and developmental context.

Keywords: communication, cooperation, development, interaction, neuroscience

Procedia PDF Downloads 235