Search results for: imaging informatics
414 The Value of Dynamic Magnetic Resonance Defecography in Assessing the Severity of Defecation Disorders
Authors: Ge Sun, Monika Trzpis, Robbert J. de Haas, Paul M. A. Broens
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Introduction: Dynamic magnetic resonance defecography is frequently used to assess defecation disorders. We aimed to investigate the usefulness of dynamic magnetic resonance defecography for assessing the severity of defecation disorder. Methods: We included patients retrospectively from our tertiary referral hospital who had undergone dynamic magnetic resonance defecography, anorectal manometry, and anal electrical sensitivity tests to assess defecation disorders between 2014 and 2020. The primary outcome was the association between the dynamic magnetic resonance defecography variables and the severity of defecation disorders. We assessed the severity of fecal incontinence and constipation with the Wexner incontinence and Agachan constipation scores. Results: Out of the 32 patients included, 24 completed the defecation questionnaire. During defecation, the M line length at magnetic resonance correlated with the Agachan score (r = 0.45, p = 0.03) and was associated with anal sphincter pressure (r=0.39, p=0.03) just before defecation. During rest and squeezing, the H line length at imaging correlated with the Wexner incontinence score (r=0.49, p=0.01 and r=0.69, p< 0.001, respectively). H line length also correlated positively with the anal electrical sensation threshold during squeezing (r=0.50, p=0.004) and during rest (r= 0.42, p=0.02). Conclusions: The M and H line lengths at dynamic magnetic resonance defecography can be used to assess the severity of constipation and fecal incontinence respectively and reflect anatomic changes of the pelvic floor. However, as these anatomic changes are generally late-stage and irreversible, anal manometry seems a better diagnostic approach to assess early and potentially reversible changes in patients with defecation disorders.Keywords: defecation disorders, dynamic magnetic resonance defecography, anorectal manometry, anal electrical sensitivity tests, H line, M line
Procedia PDF Downloads 105413 Reconstruction of Visual Stimuli Using Stable Diffusion with Text Conditioning
Authors: ShyamKrishna Kirithivasan, Shreyas Battula, Aditi Soori, Richa Ramesh, Ramamoorthy Srinath
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The human brain, among the most complex and mysterious aspects of the body, harbors vast potential for extensive exploration. Unraveling these enigmas, especially within neural perception and cognition, delves into the realm of neural decoding. Harnessing advancements in generative AI, particularly in Visual Computing, seeks to elucidate how the brain comprehends visual stimuli observed by humans. The paper endeavors to reconstruct human-perceived visual stimuli using Functional Magnetic Resonance Imaging (fMRI). This fMRI data is then processed through pre-trained deep-learning models to recreate the stimuli. Introducing a new architecture named LatentNeuroNet, the aim is to achieve the utmost semantic fidelity in stimuli reconstruction. The approach employs a Latent Diffusion Model (LDM) - Stable Diffusion v1.5, emphasizing semantic accuracy and generating superior quality outputs. This addresses the limitations of prior methods, such as GANs, known for poor semantic performance and inherent instability. Text conditioning within the LDM's denoising process is handled by extracting text from the brain's ventral visual cortex region. This extracted text undergoes processing through a Bootstrapping Language-Image Pre-training (BLIP) encoder before it is injected into the denoising process. In conclusion, a successful architecture is developed that reconstructs the visual stimuli perceived and finally, this research provides us with enough evidence to identify the most influential regions of the brain responsible for cognition and perception.Keywords: BLIP, fMRI, latent diffusion model, neural perception.
Procedia PDF Downloads 68412 Neuroimaging Markers for Screening Former NFL Players at Risk for Developing Alzheimer's Disease / Dementia Later in Life
Authors: Vijaykumar M. Baragi, Ramtilak Gattu, Gabriela Trifan, John L. Woodard, K. Meyers, Tim S. Halstead, Eric Hipple, Ewart Mark Haacke, Randall R. Benson
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NFL players, by virtue of their exposure to repetitive head injury, are at least twice as likely to develop Alzheimer's disease (AD) and dementia as the general population. Early recognition and intervention prior to onset of clinical symptoms could potentially avert/delay the long-term consequences of these diseases. Since AD is thought to have a long preclinical incubation period, the aim of the current research was to determine whether former NFL players, referred to a depression center, showed evidence of incipient dementia in their structural imaging prior to diagnosis of dementia. Thus, to identify neuroimaging markers of AD, against which former NFL players would be compared, we conducted a comprehensive volumetric analysis using a cohort of early stage AD patients (ADNI) to produce a set of brain regions demonstrating sensitivity to early AD pathology (i.e., the “AD fingerprint”). A cohort of 46 former NFL players’ brain MRIs were then interrogated using the AD fingerprint. Brain scans were done using a T1-weighted MPRAGE sequence. The Free Surfer image analysis suite (version 6.0) was used to obtain the volumetric and cortical thickness data. A total of 55 brain regions demonstrated significant atrophy or ex vacuo dilatation bilaterally in AD patients vs. healthy controls. Of the 46 former NFL players, 19 (41%) demonstrated a greater than expected number of atrophied/dilated AD regions when compared with age-matched controls, presumably reflecting AD pathology.Keywords: alzheimers, neuroimaging biomarkers, traumatic brain injury, free surfer, ADNI
Procedia PDF Downloads 154411 Effectiveness of Myofascial Release Technique in Treatment of Sacroiliac Joint Hypo-Mobility in Postnatal Women
Authors: Ahmed A. Abd El Rahim, Mohamed M. M. Essa, Magdy M. A. Shabana, Said A. Mohamed, Mohamed Ibrahim Mabrouk
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Background: Sacroiliac joint (SIJ) dysfunction is considered the main cause of pregnancy-related back pain, which may continue to persist postnatally. Myofascial release technique (MFR) is an application of low-intensity, prolonged stretch to myofascial structures to improve function by increasing the sliding properties of restricted myofascial tissues. Purpose: This study was designed to investigate the effect of MFR on postnatal SIJ hypo-mobility. Materials and Methods: Fifty postnatal women complaining of SIJ hypo-mobility participated in this study. Their ages ranged from 26 to 35 yrs., and their body mass index (BMI) didn`t exceed 30 kg/m2. They were randomly assigned to two equal groups, group A (Gr. A) and group B (Gr. B). Both groups received three sessions per week for eight successive weeks. Gr. A received a traditional physical therapy program, while Gr. B received a traditional physical therapy program in addition to MFR. Doppler imaging of vibration was utilized to measure SIJ mobility pre- and post-intervention, and an electronic digital goniometer was used to measure back flexion and extension Range of motion. Results: Findings revealed a statistical improvement in post-intervention values of SIJ mobility in addition to trunk flexion and extension ROM in Gr. B compared to Gr. A (P<0.001). Conclusion: Adding MFR to traditional physical therapy programs is highly recommended in the treatment of SIJ hypo-mobility in postnatal women.Keywords: sacroiliac hypo-mobility, sacroiliac dysfunction, myofascial release technique, traditional physical therapy, postnatal
Procedia PDF Downloads 101410 A Case of Survival with Self-Draining Haemopericardium Secondary to Stabbing
Authors: Balakrishna Valluru, Ruth Suckling
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A 16 year old male was found collapsed on the road following stab injuries to the chest and abdomen and was transported to the emergency department by ambulance. On arrival in the emergency department the patient was breathless and appeared pale. He was maintaining his airway with spontaneous breathing and had a heart rate of 122 beats per minute with a blood pressure of 83/63 mmHg. He was resuscitated initially with three units of packed red cells. Clinical examination identified three incisional wounds each measuring 2 cm. These were in the left para-sternal region, right infra-scapular region and left upper quadrant of the abdomen. The chest wound over the left parasternal area at the level of 4tth intercostal space was bleeding intermittently on leaning forwards and was relieving his breathlessness intermittently. CT imaging was performed to characterize his injuries and determine his management. CT scan of chest and abdomen showed moderate size haemopericardium with left sided haemopneumothorax. The patient underwent urgent surgical repair of the left ventricle and left anterior descending artery. He recovered without complications and was discharged from the hospital. This case highlights the fact that the potential to develop a life threatening cardiac tamponade was mitigated by the left parasternal stab wound. This injury fortuitously provided a pericardial window through which the bleeding from the injured left ventricle and left anterior descending artery could drain into the left hemithorax providing an opportunity for timely surgical intervention to repair the cardiac injuries.Keywords: stab, incisional, haemo-pericardium, haemo-pneumothorax
Procedia PDF Downloads 201409 Multi-Stage Classification for Lung Lesion Detection on CT Scan Images Applying Medical Image Processing Technique
Authors: Behnaz Sohani, Sahand Shahalinezhad, Amir Rahmani, Aliyu Aliyu
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Recently, medical imaging and specifically medical image processing is becoming one of the most dynamically developing areas of medical science. It has led to the emergence of new approaches in terms of the prevention, diagnosis, and treatment of various diseases. In the process of diagnosis of lung cancer, medical professionals rely on computed tomography (CT) scans, in which failure to correctly identify masses can lead to incorrect diagnosis or sampling of lung tissue. Identification and demarcation of masses in terms of detecting cancer within lung tissue are critical challenges in diagnosis. In this work, a segmentation system in image processing techniques has been applied for detection purposes. Particularly, the use and validation of a novel lung cancer detection algorithm have been presented through simulation. This has been performed employing CT images based on multilevel thresholding. The proposed technique consists of segmentation, feature extraction, and feature selection and classification. More in detail, the features with useful information are selected after featuring extraction. Eventually, the output image of lung cancer is obtained with 96.3% accuracy and 87.25%. The purpose of feature extraction applying the proposed approach is to transform the raw data into a more usable form for subsequent statistical processing. Future steps will involve employing the current feature extraction method to achieve more accurate resulting images, including further details available to machine vision systems to recognise objects in lung CT scan images.Keywords: lung cancer detection, image segmentation, lung computed tomography (CT) images, medical image processing
Procedia PDF Downloads 101408 Tractography Analysis of the Evolutionary Origin of Schizophrenia
Authors: Asmaa Tahiri, Mouktafi Amine
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A substantial number of traditional medical research has been put forward to managing and treating mental disorders. At the present time, to our best knowledge, it is believed that fundamental understanding of the underlying causes of the majority psychological disorders needs to be explored further to inform early diagnosis, managing symptoms and treatment. The emerging field of evolutionary psychology is a promising prospect to address the origin of mental disorders, potentially leading to more effective treatments. Schizophrenia as a topical mental disorder has been linked to the evolutionary adaptation of the human brain represented in the brain connectivity and asymmetry directly linked to humans higher brain cognition in contrast to other primates being our direct living representation of the structure and connectivity of our earliest common African ancestors. As proposed in the evolutionary psychology scientific literature the pathophysiology of schizophrenia is expressed and directly linked to altered connectivity between the Hippocampal Formation (HF) and Dorsolateral Prefrontal Cortex (DLPFC). This research paper presents the results of the use of tractography analysis using multiple open access Diffusion Weighted Imaging (DWI) datasets of healthy subjects, schizophrenia-affected subjects and primates to illustrate the relevance of the aforementioned brain regions connectivity and the underlying evolutionary changes in the human brain. Deterministic fiber tracking and streamline analysis were used to generate connectivity matrices from the DWI datasets overlaid to compute distances and highlight disconnectivity patterns in conjunction with other fiber tracking metrics; Fractional Anisotropy (FA), Mean Diffusivity (MD) and Radial Diffusivity (RD).Keywords: tractography, evolutionary psychology, schizophrenia, brain connectivity
Procedia PDF Downloads 71407 Flood Devastation Assessment Through Mapping in Nigeria-2022 using Geospatial Techniques
Authors: Hafiz Muhammad Tayyab Bhatti, Munazza Usmani
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One of nature's most destructive occurrences, floods do immense damage to communities and economic losses. Nigeria country, specifically southern Nigeria, is known for being prone to flooding. Even though periodic flooding occurs in Nigeria frequently, the floods of 2022 were the worst since those in 2012. Flood vulnerability analysis and mapping are still lacking in this region due to the very limited historical hydrological measurements and surveys on the effects of floods, which makes it difficult to develop and put into practice efficient flood protection measures. Remote sensing and Geographic Information Systems (GIS) are useful approaches to detecting, determining, and estimating the flood extent and its impacts. In this study, NOAA VIIR has been used to extract the flood extent using the flood water fraction data and afterward fused with GIS data for some zonal statistical analysis. The estimated possible flooding areas are validated using satellite imagery from the Moderate Resolution Imaging Spectroradiometer (MODIS). The goal is to map and studied flood extent, flood hazards, and their effects on the population, schools, and health facilities for each state of Nigeria. The resulting flood hazard maps show areas with high-risk levels clearly and serve as an important reference for planning and implementing future flood mitigation and control strategies. Overall, the study demonstrated the viability of using the chosen GIS and remote sensing approaches to detect possible risk regions to secure local populations and enhance disaster response capabilities during natural disasters.Keywords: flood hazards, remote sensing, damage assessment, GIS, geospatial analysis
Procedia PDF Downloads 137406 Structural Characterization of the 3D Printed Silicon Carbon/Carbon Fibers Nanocomposites
Authors: Saja M. Nabat Al-Ajrash, Charles Browning, Rose Eckerle, Li Cao
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A process that utilizes a combination of additive manufacturing (AM), a preceramic polymer, and a chopped carbon fiber precursorto fabricate Silicon Carbon/ Carbon fibers (SiC/C) composites have been developed. The study has shown a promising, cost-effective, and efficient route to fabricate complex SiC/C composites using additive manufacturing. A key part of this effort was the mapping of the material’s microstructure through the thickness of the composite. Microstructural features in the pyrolyzed composites through the successive AM layers, such as defects, crystal size and their distribution, interatomic spacing, chemical bonds, were investigated using high-resolution scanning and transmission electron microscopy. As a result, the microstructure developed in SiC/C composites after printing, cure, and pyrolysis has been successfully mapped through the thickness of the derived composites. Dense and nearly defect-free parts after polymer to ceramic conversion were observed. The ceramic matrix composite displayed three coexisting phases, including silicon carbide, silicon oxycarbide, and turbostratic carbon. Lattice fringes imaging and X-Ray Diffraction analysis showed well-defined SiC and turbostratic carbon features. The cross-sectional mapping of the printed-then-pyrolyzed structures has confirmed consistent structural and chemical features within the internal layers of the AM parts. Noteworthy, however, is that a crust-like area with high crystallinity has been observed in the first and last external layers. Not only do these crust-like regions have structural characteristics distinct from the internal layers, but they also have elemental distributions different than the internal layers.Keywords: SiC, preceramic polymer, additive manufacturing, ceramic
Procedia PDF Downloads 78405 Image Quality and Dose Optimisations in Digital and Computed Radiography X-ray Radiography Using Lumbar Spine Phantom
Authors: Elhussaien Elshiekh
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A study was performed to management and compare radiation doses and image quality during Lumbar spine PA and Lumbar spine LAT, x- ray radiography using Computed Radiography (CR) and Digital Radiography (DR). Standard exposure factors such as kV, mAs and FFD used for imaging the Lumbar spine anthropomorphic phantom obtained from average exposure factors that were used with CR in five radiology centres. Lumbar spine phantom was imaged using CR and DR systems. Entrance surface air kerma (ESAK) was calculated X-ray tube output and patient exposure factor. Images were evaluated using visual grading system based on the European Guidelines on Quality Criteria for diagnostic radiographic images. The ESAK corresponding to each image was measured at the surface of the phantom. Six experienced specialists evaluated hard copies of all the images, the image score (IS) was calculated for each image by finding the average score of the Six evaluators. The IS value also was used to determine whether an image was diagnostically acceptable. The optimum recommended exposure factors founded here for Lumbar spine PA and Lumbar spine LAT, with respectively (80 kVp,25 mAs at 100 cm FFD) and (75 kVp,15 mAs at 100 cm FFD) for CR system, and (80 kVp,15 mAs at100 cm FFD) and (75 kVp,10 mAs at 100 cm FFD) for DR system. For Lumbar spine PA, the lowest ESAK value required to obtain a diagnostically acceptable image were 0.80 mGy for DR and 1.20 mGy for CR systems. Similarly for Lumbar spine LAT projection, the lowest ESAK values to obtain a diagnostically acceptable image were 0.62 mGy for DR and 0.76 mGy for CR systems. At standard kVp and mAs values, the image quality did not vary significantly between the CR and the DR system, but at higher kVp and mAs values, the DR images were found to be of better quality than CR images. In addition, the lower limit of entrance skin dose consistent with diagnostically acceptable DR images was 40% lower than that for CR images.Keywords: image quality, dosimetry, radiation protection, optimization, digital radiography, computed radiography
Procedia PDF Downloads 50404 Utility of CT Perfusion Imaging for Diagnosis and Management of Delayed Cerebral Ischaemia Following Subarachnoid Haemorrhage
Authors: Abdalla Mansour, Dan Brown, Adel Helmy, Rikin Trivedi, Mathew Guilfoyle
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Introduction: Diagnosing delayed cerebral ischaemia (DCI) following aneurysmal subarachnoid haemorrhage (SAH) can be challenging, particularly in poor-grade patients. Objectives: This study sought to assess the value of routine CTP in identifying (or excluding) DCI and in guiding management. Methods: Eight-year retrospective neuroimaging study at a large UK neurosurgical centre. Subjects included a random sample of adult patients with confirmed aneurysmal SAH that had a CTP scan during their inpatient stay, over a 8-year period (May 2014 - May 2022). Data collected through electronic patient record and PACS. Variables included age, WFNS scale, aneurysm site, treatment, the timing of CTP, radiologist report, and DCI management. Results: Over eight years, 916 patients were treated for aneurysmal SAH; this study focused on 466 patients that were randomly selected. Of this sample, 181 (38.84%) had one or more CTP scans following brain aneurysm treatment (Total 318). The first CTP scan in each patient was performed at 1-20 days following ictus (median 4 days). There was radiological evidence of DCI in 83, and no reversible ischaemia was found in 80. Findings were equivocal in the remaining 18. Of the 103 patients treated with clipping, 49 had DCI radiological evidence, in comparison to 31 of 69 patients treated with endovascular embolization. The remaining 9 patients are either unsecured aneurysms or non-aneurysmal SAH. Of the patients with radiological evidence of DCI, 65 had a treatment change following the CTP directed at improving cerebral perfusion. In contrast, treatment was not changed for (61) patients without radiological evidence of DCI. Conclusion: CTP is a useful adjunct to clinical assessment in the diagnosis of DCI and is helpful in identifying patients that may benefit from intensive therapy and those in whom it is unlikely to be effective.Keywords: SAH, vasospasm, aneurysm, delayed cerebral ischemia
Procedia PDF Downloads 68403 Geophysical Approach in the Geological Characterization of a Dam Site: Case of the Chebabta-Dam, Meskiana, Oum El-Bouaghi
Authors: Benhammadi Hocine, Djamel Boubaya, Chaffai Hicham
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Meskiana Area is characterized by a semi-arid climate where the water supply for irrigation and industry is not sufficient as the priority goes for domestic use. To meet the increasing population growth and development, the authorities have considered building a new water retaining structure on some major temporary water streams. For this purpose Chebabta site on Oued Meskiana was chosen as the future dam site. It is large enough to store the desired volume of water. This study comes to investigate the conditions of the site and the adequacy of the ground as a foundation for the projected dam. The conditions of the site include the geological structure and mainly the presence of discontinuities in the formation on which the dam will be built, the nature of the lithologies under the foundation and the future lake, and the presence of any hazard. This site characterization is usually carried out using different methods in order to highlight any underground buried problematic structure. In this context, the different geophysical technics remain the most used ones. Three geophysical methods were used in the case of the Chebabta dam site, namely, electric survey, seismic refraction, and tomography. The choice of the technics and the location of the scan line was made on the basis of the available geological data. In this sense, profiles have been established on both banks of Oued Meskiana. The obtained results have allowed a better characterization of the geological structure, defining the limit between the surface cover and the bedrock, which is, in other words, the limit between the weathered zone and the bedrock. Their respective thicknesses were also determined by seismic refraction and electrical resistivity sounding. However, the tomography imaging technic has succeeded in positioning a fault structure passing through the right bank of the wadi.Keywords: dam site, fault, geophysic, investigation, Meskiana
Procedia PDF Downloads 88402 Optimal Parameters of Two-Color Ionizing Laser Pulses for Terahertz Generation
Authors: I. D. Laryushin, V. A. Kostin, A. A. Silaev, N. V. Vvedenskii
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Generation of broadband intense terahertz (THz) radiation attracts reasonable interest due to various applications, such as the THz time-domain spectroscopy, the probing and control of various ultrafast processes, the THz imaging with subwavelength resolution, and many others. One of the most promising methods for generating powerful and broadband terahertz pulses is based on focusing two-color femtosecond ionizing laser pulses in gases, including ambient air. For this method, the amplitudes of terahertz pulses are determined by the free-electron current density remaining in a formed plasma after the passage of the laser pulse. The excitation of this residual current density can be treated as multi-wave mixing: Аn effective generation of terahertz radiation is possible only when the frequency ratio of one-color components in the two-color pulse is close to irreducible rational fraction a/b with small odd sum a + b. This work focuses on the optimal parameters (polarizations and intensities) of laser components for the strongest THz generation. The optimal values of parameters are found numerically and analytically with the use of semiclassical approach for calculating the residual current density. For frequency ratios close to a/(a ± 1) with natural a, the strongest THz generation is shown to take place when the both laser components have circular polarizations and equal intensities. For this optimal case, an analytical formula for the residual current density was derived. For the frequency ratios such as 2/5, the two-color ionizing pulses with circularly polarized components practically do not excite the residual current density. However, the optimal parameters correspond generally to specific elliptical (not linear) polarizations of the components and intensity ratios close to unity.Keywords: broadband terahertz radiation, ionization, laser plasma, ultrashort two-color pulses
Procedia PDF Downloads 211401 Improvement of Microscopic Detection of Acid-Fast Bacilli for Tuberculosis by Artificial Intelligence-Assisted Microscopic Platform and Medical Image Recognition System
Authors: Hsiao-Chuan Huang, King-Lung Kuo, Mei-Hsin Lo, Hsiao-Yun Chou, Yusen Lin
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The most robust and economical method for laboratory diagnosis of TB is to identify mycobacterial bacilli (AFB) under acid-fast staining despite its disadvantages of low sensitivity and labor-intensive. Though digital pathology becomes popular in medicine, an automated microscopic system for microbiology is still not available. A new AI-assisted automated microscopic system, consisting of a microscopic scanner and recognition program powered by big data and deep learning, may significantly increase the sensitivity of TB smear microscopy. Thus, the objective is to evaluate such an automatic system for the identification of AFB. A total of 5,930 smears was enrolled for this study. An intelligent microscope system (TB-Scan, Wellgen Medical, Taiwan) was used for microscopic image scanning and AFB detection. 272 AFB smears were used for transfer learning to increase the accuracy. Referee medical technicians were used as Gold Standard for result discrepancy. Results showed that, under a total of 1726 AFB smears, the automated system's accuracy, sensitivity and specificity were 95.6% (1,650/1,726), 87.7% (57/65), and 95.9% (1,593/1,661), respectively. Compared to culture, the sensitivity for human technicians was only 33.8% (38/142); however, the automated system can achieve 74.6% (106/142), which is significantly higher than human technicians, and this is the first of such an automated microscope system for TB smear testing in a controlled trial. This automated system could achieve higher TB smear sensitivity and laboratory efficiency and may complement molecular methods (eg. GeneXpert) to reduce the total cost for TB control. Furthermore, such an automated system is capable of remote access by the internet and can be deployed in the area with limited medical resources.Keywords: TB smears, automated microscope, artificial intelligence, medical imaging
Procedia PDF Downloads 229400 Development of Nanoparticulate Based Chimeric Drug Delivery System Using Drug Bioconjugated Plant Virus Capsid on Biocompatible Nanoparticles
Authors: Indu Barwal, Shloka Thakur, Subhash C. Yadav
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The plant virus capsid protein based nanoparticles are extensively studied for their application in biomedical research for development of nanomedicines and drug delivery systems. We have developed a chimeric drug delivery system by controlled in vitro assembly of separately bioconjugated fluorescent dye (as reporting molecule), folic acid (as receptor binding biomolecule for targeted delivery) and doxorubicin (as anticancer drug) using modified EDC NHS chemistry on heterologously overexpressed (E. coli) capsid proteins of cowpea chlorotic mottle virus (CCMV). This chimeric vehicle was further encapsidated on gold nanoparticles (20nm) coated with 5≠ thiolated DNA probe to neutralize the positive charge of capsid proteins. This facilitates the in vitro assembly of modified capsid subunits on the gold nanoparticles to develop chimeric GNPs encapsidated targeted drug delivery system. The bioconjugation of functionalities, number of functionality on capsid subunits as well as virus like nanoparticles, structural stability and in vitro assembly were confirmed by SDS PAGE, relative absorbance, MALDI TOF, ESI-MS, Circular dichroism, intrinsic tryptophan fluorescence, zeta particle size analyzer and TEM imaging. This vehicle was stable at pH 4.0 to 8.0 suitable for many organelles targeting. This in vitro assembled chimeric plant virus like particles could be suitable for ideal drug delivery vehicles for subcutaneous cancer treatment and could be further modified for other type of cancer treatment by conjugating other functionalities (targeting, drug) on capsids.Keywords: chimeric drug delivery vehicles, bioconjugated plant, virus, capsid
Procedia PDF Downloads 493399 Cyber-Med: Practical Detection Methodology of Cyber-Attacks Aimed at Medical Devices Eco-Systems
Authors: Nir Nissim, Erez Shalom, Tomer Lancewiki, Yuval Elovici, Yuval Shahar
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Background: A Medical Device (MD) is an instrument, machine, implant, or similar device that includes a component intended for the purpose of the diagnosis, cure, treatment, or prevention of disease in humans or animals. Medical devices play increasingly important roles in health services eco-systems, including: (1) Patient Diagnostics and Monitoring; Medical Treatment and Surgery; and Patient Life Support Devices and Stabilizers. MDs are part of the medical device eco-system and are connected to the network, sending vital information to the internal medical information systems of medical centers that manage this data. Wireless components (e.g. Wi-Fi) are often embedded within medical devices, enabling doctors and technicians to control and configure them remotely. All these functionalities, roles, and uses of MDs make them attractive targets of cyber-attacks launched for many malicious goals; this trend is likely to significantly increase over the next several years, with increased awareness regarding MD vulnerabilities, the enhancement of potential attackers’ skills, and expanded use of medical devices. Significance: We propose to develop and implement Cyber-Med, a unique collaborative project of Ben-Gurion University of the Negev and the Clalit Health Services Health Maintenance Organization. Cyber-Med focuses on the development of a comprehensive detection framework that relies on a critical attack repository that we aim to create. Cyber-Med will allow researchers and companies to better understand the vulnerabilities and attacks associated with medical devices as well as providing a comprehensive platform for developing detection solutions. Methodology: The Cyber-Med detection framework will consist of two independent, but complementary detection approaches: one for known attacks, and the other for unknown attacks. These modules incorporate novel ideas and algorithms inspired by our team's domains of expertise, including cyber security, biomedical informatics, and advanced machine learning, and temporal data mining techniques. The establishment and maintenance of Cyber-Med’s up-to-date attack repository will strengthen the capabilities of Cyber-Med’s detection framework. Major Findings: Based on our initial survey, we have already found more than 15 types of vulnerabilities and possible attacks aimed at MDs and their eco-system. Many of these attacks target individual patients who use devices such pacemakers and insulin pumps. In addition, such attacks are also aimed at MDs that are widely used by medical centers such as MRIs, CTs, and dialysis engines; the information systems that store patient information; protocols such as DICOM; standards such as HL7; and medical information systems such as PACS. However, current detection tools, techniques, and solutions generally fail to detect both the known and unknown attacks launched against MDs. Very little research has been conducted in order to protect these devices from cyber-attacks, since most of the development and engineering efforts are aimed at the devices’ core medical functionality, the contribution to patients’ healthcare, and the business aspects associated with the medical device.Keywords: medical device, cyber security, attack, detection, machine learning
Procedia PDF Downloads 356398 High-Frequency Modulation of Light-Emitting Diodes for New Ultraviolet Communications
Authors: Meng-Chyi Wu, Bonn Lin, Jyun-Hao Liao, Chein-Ju Chen, Yu-Cheng Jhuang, Mau-Phon Houng, Fang-Hsing Wang, Min-Chu Liu, Cheng-Fu Yang, Cheng-Shong Hong
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Since the use of wireless communications has become critical nowadays, the available RF spectrum has become limited. Ultraviolet (UV) communication system can alleviate the spectrum constraint making UV communication system a potential alternative to future communication demands. Also, UV links can provide faster communication rate and can be used in combination with existing RF communication links, providing new communications diversity with higher user capacity. The UV region of electromagnetic spectrum has been of interest to detector, imaging and communication technologies because the stratospheric ozone layer effectively absorbs some solar UV radiation from reaching the earth surface. The wavebands where most of UV radiation is absorbed by the ozone are commonly known as the solar blind region. By operating in UV-C band (200-280 nm) the communication system can minimize the transmission power consumption since it will have less radiation noise. UV communication uses the UV ray as the medium. Electric signal is carried on this band after being modulated and then be transmitted within the atmosphere as channel. Though the background noise of UV-C communication is very low owing to the solar-blind feature, it leads to a large propagation loss. The 370 nm UV provides a much lower propagation loss than that the UV-C does and the recent device technology for UV source on this band is more mature. The fabricated 370 nm AlGaN light-emitting diodes (LEDs) with an aperture size of 45 m exhibit a modulation bandwidth of 165 MHz at 30 mA and a high power of 7 W/cm2 at 230 A/cm2. In order to solve the problem of low power in single UV LED, a UV LED array is presented in.Keywords: ultraviolet (UV) communication, light-emitting diodes (LEDs), modulation bandwidth, LED array, 370 nm
Procedia PDF Downloads 414397 Profiling of the Cell-Cycle Related Genes in Response to Efavirenz, a Non-Nucleoside Reverse Transcriptase Inhibitor in Human Lung Cancer
Authors: Rahaba Marima, Clement Penny
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The Health-related quality of life (HRQoL) for HIV positive patients has improved since the introduction of the highly active antiretroviral treatment (HAART). However, in the present HAART era, HIV co-morbidities such as lung cancer, a non-AIDS (NAIDS) defining cancer have been documented to be on the rise. Under normal physiological conditions, cells grow, repair and proliferate through the cell-cycle as cellular homeostasis is important in the maintenance and proper regulation of tissues and organs. Contrarily, the deregulation of the cell-cycle is a hallmark of cancer, including lung cancer. The association between lung cancer and the use of HAART components such as Efavirenz (EFV) is poorly understood. This study aimed at elucidating the effects of EFV on the cell-cycle genes’ expression in lung cancer. For this purpose, the human cell-cycle gene array composed of 84 genes was evaluated on both normal lung fibroblasts (MRC-5) cells and adenocarcinoma (A549) lung cells, in response to 13µM EFV or 0.01% vehicle. The ±2 up or down fold change was used as a basis of target selection, with p < 0.05. Additionally, RT-qPCR was done to validate the gene array results. Next, In-silico bio-informatics tools, Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), Reactome, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Ingenuity Pathway Analysis (IPA) were used for gene/gene interaction studies as well as to map the molecular and biological pathways influenced by the identified targets. Interestingly, the DNA damage response (DDR) pathway genes such as p53, Ataxia telangiectasia mutated and Rad3 related (ATR), Growth arrest and DNA damage inducible alpha (GADD45A), HUS1 checkpoint homolog (HUS1) and Role of radiation (RAD) genes were shown to be upregulated following EFV treatment, as revealed by STRING analysis. Additionally, functional enrichment analysis by the KEGG pathway revealed that most of the differentially expressed gene targets function at the cell-cycle checkpoint such as p21, Aurora kinase B (AURKB) and Mitotic Arrest Deficient-Like 2 (MAD2L2). Core analysis by IPA revealed that p53 downstream targets such as survivin, Bcl2, and cyclin/cyclin dependent kinases (CDKs) complexes are down-regulated, following exposure to EFV. Furthermore, Reactome analysis showed a significant increase in cellular response to stress genes, DNA repair genes, and apoptosis genes, as observed in both normal and cancerous cells. These findings implicate the genotoxic effects of EFV on lung cells, provoking the DDR pathway. Notably, the constitutive expression of this pathway (DDR) often leads to uncontrolled cell proliferation and eventually tumourigenesis, which could be the attribute of HAART components’ (such as EFV) effect on human cancers. Targeting the cell-cycle and its regulation holds a promising therapeutic intervention to the potential HAART associated carcinogenesis, particularly lung cancer.Keywords: cell-cycle, DNA damage response, Efavirenz, lung cancer
Procedia PDF Downloads 156396 Biophysical Features of Glioma-Derived Extracellular Vesicles as Potential Diagnostic Markers
Authors: Abhimanyu Thakur, Youngjin Lee
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Glioma is a lethal brain cancer whose early diagnosis and prognosis are limited due to the dearth of a suitable technique for its early detection. Current approaches, including magnetic resonance imaging (MRI), computed tomography (CT), and invasive biopsy for the diagnosis of this lethal disease, hold several limitations, demanding an alternative method. Recently, extracellular vesicles (EVs) have been used in numerous biomarker studies, majorly exosomes and microvesicles (MVs), which are found in most of the cells and biofluids, including blood, cerebrospinal fluid (CSF), and urine. Remarkably, glioma cells (GMs) release a high number of EVs, which are found to cross the blood-brain-barrier (BBB) and impersonate the constituents of parent GMs including protein, and lncRNA; however, biophysical properties of EVs have not been explored yet as a biomarker for glioma. We isolated EVs from cell culture conditioned medium of GMs and regular primary culture, blood, and urine of wild-type (WT)- and glioma mouse models, and characterized by nano tracking analyzer, transmission electron microscopy, immunogold-EM, and differential light scanning. Next, we measured the biophysical parameters of GMs-EVs by using atomic force microscopy. Further, the functional constituents of EVs were examined by FTIR and Raman spectroscopy. Exosomes and MVs-derived from GMs, blood, and urine showed distinction biophysical parameters (roughness, adhesion force, and stiffness) and different from that of regular primary glial cells, WT-blood, and -urine, which can be attributed to the characteristic functional constituents. Therefore, biophysical features can be potential diagnostic biomarkers for glioma.Keywords: glioma, extracellular vesicles, exosomes, microvesicles, biophysical properties
Procedia PDF Downloads 142395 Malignant Idiopathic Intracranial Hypertension Revealed a Hidden Primary Spinal Leptomeningeal Medulloblastoma
Authors: Naim Izet Kajtazi
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Context: Frequently, the cause of raised intracranial pressure remains unresolved and rarely is related to spinal tumors, moreover less to spinal medulloblastoma without primary brain focus. Process: An 18-year-old woman had a 3-month history of headaches and impaired vision. Neurological examination revealed bilateral sixth cranial nerve palsies with bilateral papilloedema of grade III. No focal brain or spine lesion was found on imaging. Consecutive lumbar punctures showed high opening pressure and subsequent increasing protein level. The meningeal biopsy was negative. At one point, she developed an increasing headache, vomiting and back pain. Spine MRI showed diffuse nodular leptomeningeal enhancement with the largest nodule at T6–T7. Malignant cells were detected in cerebrospinal fluid. She underwent laminectomy with excisional biopsy, and pathology showed medulloblastoma WHO grade IV. Outcome: She was treated with chemotherapy and craniospinal irradiation and made a good recovery. Relevance: Primary spinal leptomeningeal medulloblastoma is extremely rare, especially without primary brain focus, but may cause increased intracranial pressure, even in the early microscopic phases, and it should be considered in the differential diagnosis if conventional and aggressive treatment of idiopathic intracranial hypertension fails. We assume that arachnoiditis from tumor seeding caused increased intracranial pressure. Appropriate neurosurgical intervention and surgical biopsy are mandated if a suspicious lesion is detected. Consider proper rescreening of the whole neuroaxis in refractory cases of intracranial hypertension.Keywords: CNS infection, IIH, headache, primary spinal leptomeningeal medulloblastoma
Procedia PDF Downloads 66394 Mechanisms and Regulation of the Bi-directional Motility of Mitotic Kinesin Nano-motors
Authors: Larisa Gheber
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Mitosis is an essential process by which duplicated genetic information is transmitted from mother to daughter cells. Incorrect chromosome segregation during mitosis can lead to genetic diseases, chromosome instability and cancer. This process is mediated by a dynamic microtubule-based intracellular structure, the mitotic spindle. One of the major factors that govern the mitotic spindle dynamics are the kinesin-5 biological nano motors that were believed to move unidirectionally on the microtubule filaments, using ATP hydrolysis, thus performing essential functions in mitotic spindle dynamics. Surprisingly, several reports from our and other laboratories have demonstrated that some kinesin-5 motors are bi-directional: they move in minus-end direction on the microtubules as single-molecules and can switch directionality under a number of conditions. These findings broke a twenty-five-years old dogma regarding kinesin directionality (1, 2). The mechanism of this bi-directional motility and its physiological significance remain unclear. To address this unresolved problem, we apply an interdisciplinary approach combining live cell imaging, biophysical single molecule, and structural experiments to examine the activity of these motors and their mutated variants in vivo and in vitro. Our data shows that factors such as protein phosphorylation (3, 4), motor clustering on the microtubules (5, 6) and structural elements (7, 8) regulate the bi-directional motility of kinesin motors. We also show, using Cryo-EM, that bi-directional kinesin motors obtain non-canonical microtubule binding, which is essential to their special motile properties and intracellular functions. We will discuss the implication of these findings to mechanism bi-directional motility and physiological roles in mitosis.Keywords: mitosis, cancer, kinesin, microtubules, biochemistry, biophysics
Procedia PDF Downloads 81393 External Vacuum Dressing: Optimising Non-Operative Management of Flail Sternum Post CPR
Authors: Nicholas Bayfield, Mark Newman
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Case Presentation: A 48-year-old male was brought in by ambulance after an out-of-hospital cardiac arrest, with 20 minutes of good-quality cardiopulmonary resuscitation in the community. Return of spontaneous circulation was achieved with defibrillation, revealing an inferior ST-elevation myocardial infarction. He was revascularized emergently in the cath lab and stabilised. Following the procedure, he was noted to have paradoxical respiratory movements of the sternum and high oxygen requirements. CT imaging demonstrated a flail chest with bilateral anterior rib 1-7 fractures as well as a large left-sided extra-pleural haematoma and small haemopneumothorax, secondary to CPR. The patient’s ventilation was stabilised with oxygen via a high-flow humidifier. Pain relief was provided. The anatomy of his rib fractures was not easily amenable to operative fixation. In addition, he was considered to be a high-risk operative candidate due to his recent arrest. He was managed thus non-operatively with an external vacuum dressing applied to the anterior chest wall to minimise respiratory compromise and minimise pain from the motion around the rib fracture sites. Non-operative management was successful, and the patient was reviewed one month later. The paradoxical sternal movement had abated. Discussion: External vacuum dressing has been trialled for non-operative management of rib fractures with varying success. It provides an external brace to minimise fracture site movement during respiration and coughing, thus minimising pain. This modality should be considered a low-cost, high-reward adjunct to non-operative management of bony thoracic trauma.Keywords: thoracic surgery, thoracic trauma, rib fractures, negative pressure dressing
Procedia PDF Downloads 154392 Study Employed a Computer Model and Satellite Remote Sensing to Evaluate the Temporal and Spatial Distribution of Snow in the Western Hindu Kush Region of Afghanistan
Authors: Noori Shafiqullah
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Millions of people reside downstream of river basins that heavily rely on snowmelt originating from the Hindu Kush (HK) region. Snowmelt plays a critical role as a primary water source in these areas. This study aimed to evaluate snowfall and snowmelt characteristics in the HK region across altitudes ranging from 2019m to 4533m. To achieve this, the study employed a combination of remote sensing techniques and the Snow Model (SM) to analyze the spatial and temporal distribution of Snow Water Equivalent (SWE). By integrating the simulated Snow-cover Area (SCA) with data from the Moderate Resolution Imaging Spectroradiometer (MODIS), the study optimized the Precipitation Gradient (PG), snowfall assessment, and the degree-day factor (DDF) for snowmelt distribution. Ground observed data from various elevations were used to calculate a temperature lapse rate of -7.0 (°C km-1). Consequently, the DDF value was determined as 3 (mm °C-1 d-1) for altitudes below 3000m and 3 to 4 (mm °C-1 d-1) for higher altitudes above 3000m. Moreover, the distribution of precipitation varies with elevation, with the PG being 0.001 (m-1) at lower elevations below 4000m and 0 (m-1) at higher elevations above 4000m. This study successfully utilized the SM to assess SCA and SWE by incorporating the two optimized parameters. The analysis of simulated SCA and MODIS data yielded coefficient determinations of R2, resulting in values of 0.95 and 0.97 for the years 2014-2015, 2015-2016, and 2016-2017, respectively. These results demonstrate that the SM is a valuable tool for managing water resources in mountainous watersheds such as the HK, where data scarcity poses a challenge."Keywords: improved MODIS, experiment, snow water equivalent, snowmelt
Procedia PDF Downloads 69391 Replicating Brain’s Resting State Functional Connectivity Network Using a Multi-Factor Hub-Based Model
Authors: B. L. Ho, L. Shi, D. F. Wang, V. C. T. Mok
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The brain’s functional connectivity while temporally non-stationary does express consistency at a macro spatial level. The study of stable resting state connectivity patterns hence provides opportunities for identification of diseases if such stability is severely perturbed. A mathematical model replicating the brain’s spatial connections will be useful for understanding brain’s representative geometry and complements the empirical model where it falls short. Empirical computations tend to involve large matrices and become infeasible with fine parcellation. However, the proposed analytical model has no such computational problems. To improve replicability, 92 subject data are obtained from two open sources. The proposed methodology, inspired by financial theory, uses multivariate regression to find relationships of every cortical region of interest (ROI) with some pre-identified hubs. These hubs acted as representatives for the entire cortical surface. A variance-covariance framework of all ROIs is then built based on these relationships to link up all the ROIs. The result is a high level of match between model and empirical correlations in the range of 0.59 to 0.66 after adjusting for sample size; an increase of almost forty percent. More significantly, the model framework provides an intuitive way to delineate between systemic drivers and idiosyncratic noise while reducing dimensions by more than 30 folds, hence, providing a way to conduct attribution analysis. Due to its analytical nature and simple structure, the model is useful as a standalone toolkit for network dependency analysis or as a module for other mathematical models.Keywords: functional magnetic resonance imaging, multivariate regression, network hubs, resting state functional connectivity
Procedia PDF Downloads 151390 Impact of Aging on Fatigue Performance of Novel Hybrid HMA
Authors: Faizan Asghar, Mohammad Jamal Khattak
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Aging, in general, refers to changes in rheological characteristics of asphalt mixture due to changes in chemical composition over the course of construction and service life of the pavement. The main goal of this study was to investigate the impact of oxidation on fatigue characteristics of a novel HMA composite fabricated with a combination of crumb rubber (CRM) and polyvinyl alcohol (PVA) fiber subject to aging of 7 and 14 days. A flexural beam fatigue test was performed to evaluate several characteristics of control, CRM modified, PVA reinforced, and novel rubber-fiber HMA composite. Experimental results revealed that aging had a significant impact on the fatigue performance of novel HMA composite. It was found that a suitable proportion of CRM and PVA radically affected the performance of novel rubber-fiber HMA in resistance to fracture and fatigue cracking when subjected to long-term aging. The developed novel HMA composite containing 2% CRM and 0.2% PVA presented around 29 times higher resistance to fatigue cracking for a period of 7 days of aging. To develop a cumulative plastic deformation level of 250 micros, such a mixture required over 50 times higher cycles than control HMA. Moreover, the crack propagation rate was reduced by over 90%, with over 12 times higher energy required to propagate a unit crack length in such a mixture compared to conventional HMA. Further, digital imaging correlation analyses revealed a more twisted and convoluted fracture path and higher strain distribution in rubber-fiber HMA composite. The fatigue performance after long-term aging of such novel HMA composite explicitly validates the ability to withstand load repetition that could lead to an extension in the service life of pavement infrastructure and reduce taxpayers’ dollars spent.Keywords: crumb rubber, PVA fibers, dry process, aging, performance testing, fatigue life
Procedia PDF Downloads 66389 Grassland Phenology in Different Eco-Geographic Regions over the Tibetan Plateau
Authors: Jiahua Zhang, Qing Chang, Fengmei Yao
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Studying on the response of vegetation phenology to climate change at different temporal and spatial scales is important for understanding and predicting future terrestrial ecosystem dynamics andthe adaptation of ecosystems to global change. In this study, the Moderate Resolution Imaging Spectroradiometer (MODIS) Normalized Difference Vegetation Index (NDVI) dataset and climate data were used to analyze the dynamics of grassland phenology as well as their correlation with climatic factors in different eco-geographic regions and elevation units across the Tibetan Plateau. The results showed that during 2003–2012, the start of the grassland greening season (SOS) appeared later while the end of the growing season (EOS) appeared earlier following the plateau’s precipitation and heat gradients from southeast to northwest. The multi-year mean value of SOS showed differences between various eco-geographic regions and was significantly impacted by average elevation and regional average precipitation during spring. Regional mean differences for EOS were mainly regulated by mean temperature during autumn. Changes in trends of SOS in the central and eastern eco-geographic regions were coupled to the mean temperature during spring, advancing by about 7d/°C. However, in the two southwestern eco-geographic regions, SOS was delayed significantly due to the impact of spring precipitation. The results also showed that the SOS occurred later with increasing elevation, as expected, with a delay rate of 0.66 d/100m. For 2003–2012, SOS showed an advancing trend in low-elevation areas, but a delayed trend in high-elevation areas, while EOS was delayed in low-elevation areas, but advanced in high-elevation areas. Grassland SOS and EOS changes may be influenced by a variety of other environmental factors in each eco-geographic region.Keywords: grassland, phenology, MODIS, eco-geographic regions, elevation, climatic factors, Tibetan Plateau
Procedia PDF Downloads 322388 Studying Second Language Development from a Complex Dynamic Systems Perspective
Authors: L. Freeborn
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This paper discusses the application of complex dynamic system theory (DST) to the study of individual differences in second language development. This transdisciplinary framework allows researchers to view the trajectory of language development as a dynamic, non-linear process. A DST approach views language as multi-componential, consisting of multiple complex systems and nested layers. These multiple components and systems continuously interact and influence each other at both the macro- and micro-level. Dynamic systems theory aims to explain and describe the development of the language system, rather than make predictions about its trajectory. Such a holistic and ecological approach to second language development allows researchers to include various research methods from neurological, cognitive, and social perspectives. A DST perspective would involve in-depth analyses as well as mixed methods research. To illustrate, a neurobiological approach to second language development could include non-invasive neuroimaging techniques such as electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) to investigate areas of brain activation during language-related tasks. A cognitive framework would further include behavioural research methods to assess the influence of intelligence and personality traits, as well as individual differences in foreign language aptitude, such as phonetic coding ability and working memory capacity. Exploring second language development from a DST approach would also benefit from including perspectives from the field of applied linguistics, regarding the teaching context, second language input, and the role of affective factors such as motivation. In this way, applying mixed research methods from neurobiological, cognitive, and social approaches would enable researchers to have a more holistic view of the dynamic and complex processes of second language development.Keywords: dynamic systems theory, mixed methods, research design, second language development
Procedia PDF Downloads 135387 Bilateral Hemodynamic Responses on Prefrontal Cortex during Voluntary Regulated Breathing (Pranayama) Practices: A Near Infrared Spectroscopy Study
Authors: Singh Deepeshwar, Suhas Vinchurkar
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Similar to neuroimaging findings through functional magnetic resonance imaging (fMRI) assessing regional cerebral blood oxygenation, the functional near infrared spectroscopy (fNIRS) has also been used to assess hemodynamic responses in the imaged region of the brain. The present study assessed hemodynamic responses in terms of changes in oxygenation (HbO), deoxygenation (HbR) and total hemoglobin (THb) on the prefrontal cortex (PFC), bilaterally, using fNIRS in 10 participants who performed three voluntary regulated breathing (pranayama) practices viz. (i) Left nostril breathing (LNB), (ii) Right nostril breathing (RNB); and (iii) Alternating nostril breathing (ANB) and compared with normal breathing as baseline (BS). For this, we used 64 channel NIRS system covering left and the right prefrontal cortex. The normal breathing kept as baseline (BS) measures as regressors in the investigation of hemodynamic responses when compared with LNB, RNB and ANB. In the results, we found greater oxygenation in contralateral side i.e., higher activation on the left prefrontal cortex (lPFC) during RNB, and right prefrontal cortex (rPFC) during LNB, whereas ANB showed greater deoxygenation responses on both sides of PFC. Interestingly, LNB showed increased oxygenation on ipsilateral side i.e., lPFC but not during RNB. This suggests that voluntary regulated breathing produced an immediate effect not only on contralateral but ipsilateral sides of the brain as well. In conclusion, breathing practices are tightly coupled to cerebral rhythms of alternating cerebral hemispheric activity during particular nostril breathing. These results of the specific nostril breathing do not support previous findings of contralateral hemispheric improvement while left or right nostril breathing only.Keywords: hemodynamic responses, brain, pranayama, voluntary regulated breathing practices, prefrontal cortex
Procedia PDF Downloads 227386 A High Content Screening Platform for the Accurate Prediction of Nephrotoxicity
Authors: Sijing Xiong, Ran Su, Lit-Hsin Loo, Daniele Zink
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The kidney is a major target for toxic effects of drugs, industrial and environmental chemicals and other compounds. Typically, nephrotoxicity is detected late during drug development, and regulatory animal models could not solve this problem. Validated or accepted in silico or in vitro methods for the prediction of nephrotoxicity are not available. We have established the first and currently only pre-validated in vitro models for the accurate prediction of nephrotoxicity in humans and the first predictive platforms based on renal cells derived from human pluripotent stem cells. In order to further improve the efficiency of our predictive models, we recently developed a high content screening (HCS) platform. This platform employed automated imaging in combination with automated quantitative phenotypic profiling and machine learning methods. 129 image-based phenotypic features were analyzed with respect to their predictive performance in combination with 44 compounds with different chemical structures that included drugs, environmental and industrial chemicals and herbal and fungal compounds. The nephrotoxicity of these compounds in humans is well characterized. A combination of chromatin and cytoskeletal features resulted in high predictivity with respect to nephrotoxicity in humans. Test balanced accuracies of 82% or 89% were obtained with human primary or immortalized renal proximal tubular cells, respectively. Furthermore, our results revealed that a DNA damage response is commonly induced by different PTC-toxicants with diverse chemical structures and injury mechanisms. Together, the results show that the automated HCS platform allows efficient and accurate nephrotoxicity prediction for compounds with diverse chemical structures.Keywords: high content screening, in vitro models, nephrotoxicity, toxicity prediction
Procedia PDF Downloads 312385 Clinical and Radiological Features of Adenomyosis and Its Histopathological Correlation
Authors: Surabhi Agrawal Kohli, Sunita Gupta, Esha Khanuja, Parul Garg, P. Gupta
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Background: Adenomyosis is a common gynaecological condition that affects the menstruating women. Uterine enlargement, dysmenorrhoea, and menorrhagia are regarded as the cardinal clinical symptoms of adenomyosis. Classically it was thought, compared with ultrasonography, when adenomyosis is suspected, MRI enables more accurate diagnosis of the disease. Materials and Methods: 172 subjects were enrolled after an informed consent that had complaints of HMB, dyspareunia, dysmenorrhea, and chronic pelvic pain. Detailed history of the enrolled subjects was taken, followed by a clinical examination. These patients were then subjected to TVS where myometrial echo texture, presence of myometrial cysts, blurring of endomyometrial junction was noted. MRI was followed which noted the presence of junctional zone thickness and myometrial cysts. After hysterectomy, histopathological diagnosis was obtained. Results: 78 participants were analysed. The mean age was 44.2 years. 43.5% had parity of 4 or more. heavy menstrual bleeding (HMB) was present in 97.8% and dysmenorrhea in 93.48 % of HPE positive patient. Transvaginal sonography (TVS) and MRI had a sensitivity of 89.13% and 80.43%, specificity of 90.62% and 84.37%, positive likelihood ratio of 9.51 and 5.15, negative likelihood ratio of 0.12 and 0.23, positive predictive value of 93.18% and 88.1%, negative predictive value of 85.29% and 75% and a diagnostic accuracy of 89.74% and 82.5%. Comparison of sensitivity (p=0.289) and specificity (p=0.625) showed no statistically significant difference between TVS and MRI. Conclusion: Prevalence of 30.23%. HMB with dysmenorrhoea and chronic pelvic pain helps in diagnosis. TVS (Endomyometrial junction blurring) is both sensitive and specific in diagnosing adenomyosis without need for additional diagnostic tool. Both TVS and MRI are equally efficient, however because of certain additional advantages of TVS over MRI, it may be used as the first choice of imaging. MRI may be used additionally in difficult cases as well as in patients with existing co-pathologies.Keywords: adenomyosis, heavy menstrual bleeding, MRI, TVS
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