Search results for: model-free damage detection
142 Effects of Virtual Reality Treadmill Training on Gait and Balance Performance of Patients with Stroke: Review
Authors: Hanan Algarni
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Background: Impairment of walking and balance skills has negative impact on functional independence and community participation after stroke. Gait recovery is considered a primary goal in rehabilitation by both patients and physiotherapists. Treadmill training coupled with virtual reality technology is a new emerging approach that offers patients with feedback, open and random skills practice while walking and interacting with virtual environmental scenes. Objectives: To synthesize the evidence around the effects of the VR treadmill training on gait speed and balance primarily, functional independence and community participation secondarily in stroke patients. Methods: Systematic review was conducted; search strategy included electronic data bases: MEDLINE, AMED, Cochrane, CINAHL, EMBASE, PEDro, Web of Science, and unpublished literature. Inclusion criteria: Participant: adult >18 years, stroke, ambulatory, without severe visual or cognitive impartments. Intervention: VR treadmill training alone or with physiotherapy. Comparator: any other interventions. Outcomes: gait speed, balance, function, community participation. Characteristics of included studies were extracted for analysis. Risk of bias assessment was performed using Cochrane's ROB tool. Narrative synthesis of findings was undertaken and summary of findings in each outcome was reported using GRADEpro. Results: Four studies were included involving 84 stroke participants with chronic hemiparesis. Interventions intensity ranged (6-12 sessions, 20 minutes-1 hour/session). Three studies investigated the effects on gait speed and balance. 2 studies investigated functional outcomes and one study assessed community participation. ROB assessment showed 50% unclear risk of selection bias and 25% of unclear risk of detection bias across the studies. Heterogeneity was identified in the intervention effects at post training and follow up. Outcome measures, training intensity and durations also varied across the studies, grade of evidence was low for balance, moderate for speed and function outcomes, and high for community participation. However, it is important to note that grading was done on few numbers of studies in each outcome. Conclusions: The summary of findings suggests positive and statistically significant effects (p<0.05) of VR treadmill training compared to other interventions on gait speed, dynamic balance skills, function and participation directly after training. However, the effects were not sustained at follow up in two studies (2 weeks-1 month) and other studies did not perform follow up measurements. More RCTs with larger sample sizes and higher methodological quality are required to examine the long term effects of VR treadmill effects on function independence and community participation after stroke, in order to draw conclusions and produce stronger robust evidence.Keywords: virtual reality, treadmill, stroke, gait rehabilitation
Procedia PDF Downloads 274141 Temperature Dependence of the Optoelectronic Properties of InAs(Sb)-Based LED Heterostructures
Authors: Antonina Semakova, Karim Mynbaev, Nikolai Bazhenov, Anton Chernyaev, Sergei Kizhaev, Nikolai Stoyanov
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At present, heterostructures are used for fabrication of almost all types of optoelectronic devices. Our research focuses on the optoelectronic properties of InAs(Sb) solid solutions that are widely used in fabrication of light emitting diodes (LEDs) operating in middle wavelength infrared range (MWIR). This spectral range (2-6 μm) is relevant for laser diode spectroscopy of gases and molecules, for systems for the detection of explosive substances, medical applications, and for environmental monitoring. The fabrication of MWIR LEDs that operate efficiently at room temperature is mainly hindered by the predominance of non-radiative Auger recombination of charge carriers over the process of radiative recombination, which makes practical application of LEDs difficult. However, non-radiative recombination can be partly suppressed in quantum-well structures. In this regard, studies of such structures are quite topical. In this work, electroluminescence (EL) of LED heterostructures based on InAs(Sb) epitaxial films with the molar fraction of InSb ranging from 0 to 0.09 and multi quantum-well (MQW) structures was studied in the temperature range 4.2-300 K. The growth of the heterostructures was performed by metal-organic chemical vapour deposition on InAs substrates. On top of the active layer, a wide-bandgap InAsSb(Ga,P) barrier was formed. At low temperatures (4.2-100 K) stimulated emission was observed. As the temperature increased, the emission became spontaneous. The transition from stimulated emission to spontaneous one occurred at different temperatures for structures with different InSb contents in the active region. The temperature-dependent carrier lifetime, limited by radiative recombination and the most probable Auger processes (for the materials under consideration, CHHS and CHCC), were calculated within the framework of the Kane model. The effect of various recombination processes on the carrier lifetime was studied, and the dominant role of Auger processes was established. For MQW structures quantization energies for electrons, light and heavy holes were calculated. A characteristic feature of the experimental EL spectra of these structures was the presence of peaks with energy different from that of calculated optical transitions between the first quantization levels for electrons and heavy holes. The obtained results showed strong effect of the specific electronic structure of InAsSb on the energy and intensity of optical transitions in nanostructures based on this material. For the structure with MQWs in the active layer, a very weak temperature dependence of EL peak was observed at high temperatures (>150 K), which makes it attractive for fabricating temperature-resistant gas sensors operating in the middle-infrared range.Keywords: Electroluminescence, InAsSb, light emitting diode, quantum wells
Procedia PDF Downloads 212140 Aerosol Chemical Composition in Urban Sites: A Comparative Study of Lima and Medellin
Authors: Guilherme M. Pereira, Kimmo Teinïla, Danilo Custódio, Risto Hillamo, Célia Alves, Pérola de C. Vasconcellos
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South American large cities often present serious air pollution problems and their atmosphere composition is influenced by a variety of emissions sources. The South American Emissions Megacities, and Climate project (SAEMC) has focused on the study of emissions and its influence on climate in the South American largest cities and it also included Lima (Peru) and Medellin (Colombia), sites where few studies of the genre were done. Lima is a coastal city with more than 8 million inhabitants and the second largest city in South America. Medellin is a 2.5 million inhabitants city and second largest city in Colombia; it is situated in a valley. The samples were collected in quartz fiber filters in high volume samplers (Hi-Vol), in 24 hours of sampling. The samples were collected in intensive campaigns in both sites, in July, 2010. Several species were determined in the aerosol samples of Lima and Medellin. Organic and elemental carbon (OC and EC) in thermal-optical analysis; biomass burning tracers (levoglucosan - Lev, mannosan - Man and galactosan - Gal) in high-performance anion exchange ion chromatography with mass spectrometer detection; water soluble ions in ion chromatography. The average particulate matter was similar for both campaigns, the PM10 concentrations were above the recommended by World Health Organization (50 µg m⁻³ – daily limit) in 40% of the samples in Medellin, while in Lima it was above that value in 15% of the samples. The average total ions concentration was higher in Lima (17450 ng m⁻³ in Lima and 3816 ng m⁻³ in Medellin) and the average concentrations of sodium and chloride were higher in this site, these species also had better correlations (Pearson’s coefficient = 0,63); suggesting a higher influence of marine aerosol in the site due its location in the coast. Sulphate concentrations were also much higher at Lima site; which may be explained by a higher influence of marine originated sulphate. However, the OC, EC and monosaccharides average concentrations were higher at Medellin site; this may be due to the lower dispersion of pollutants due to the site’s location and a larger influence of biomass burning sources. The levoglucosan average concentration was 95 ng m⁻³ for Medellin and 16 ng m⁻³ and OC was well correlated with levoglucosan (Pearson’s coefficient = 0,86) in Medellin; suggesting a higher influence of biomass burning over the organic aerosol in this site. The Lev/Man ratio is often related to the type of biomass burned and was close to 18, similar to the observed in previous studies done at biomass burning impacted sites in the Amazon region; backward trajectories also suggested the transport of aerosol from that region. Biomass burning appears to have a larger influence on the air quality in Medellin, in addition the vehicular emissions; while Lima showed a larger influence of marine aerosol during the study period.Keywords: aerosol transport, atmospheric particulate matter, biomass burning, SAEMC project
Procedia PDF Downloads 263139 Immune Responses and Pathological Manifestations in Chicken to Oral Infection with Salmonella typhimurium
Authors: Mudasir Ahmad Syed, Raashid Ahmd Wani, Mashooq Ahmad Dar, Uneeb Urwat, Riaz Ahmad Shah, Nazir Ahmad Ganai
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Salmonella enterica serovar Typhimurium (Salmonella Typhimurium) is a primary avian pathogen responsible for severe intestinal pathology in younger chickens and economic losses. However, the Salmonella Typhimurium is also able to cause infection in humans, described by typhoid fever and acute gastro-intestinal disease. A study was conducted at days to investigate pathological, histopathological, haemato-biochemical, immunological and expression kinetics of NRAMP (natural resistance associated macrophage protein) gene family (NRAMP1 and NRAMP2) in broiler chickens following experimental infection of Salmonella Typhimurium at 0,1,3,5,7,9,11,13 and 15 days respectively. Infection was developed in birds through oral route at 2×108 CFU/ml. Clinical symptoms appeared 4 days post infection (dpi) and after one-week birds showed progressive weakness, anorexia, diarrhea and lowering of head. On postmortem examination, liver showed congestion, hemorrhage and necrotic foci on surface, while as spleen, lungs and intestines revealed congestion and hemorrhages. Histopathological alterations were principally observed in liver in second week post infection. Changes in liver comprised of congestion, areas of necrosis, reticular endothelial hyperplasia in association with mononuclear cell and heterophilic infiltration. Hematological studies confirm a significant decrease (P<0.05) in RBC count, Hb concentration and PCV. White blood cell count showed significant increase throughout the experimental study. An increase in heterophils was found up to 7dpi and a decreased pattern was observed afterwards. Initial lymphopenia followed by lymphocytosis was found in infected chicks. Biochemical studies showed a significant increase in glucose, AST and ALT concentration and a significant decrease (P<0.05) in total protein and albumin level in the infected group. Immunological studies showed higher titers of IgG in infected group as compared to control group. The real time gene expression of NRAMPI and NRAMP2 genes increased significantly (P<0.05) in infected group as compared to controls. The peak expression of NRAMP1 gene was seen in liver, spleen and caecum of infected birds at 3dpi, 5dpi and 7dpi respectively, while as peak expression of NRAMP2 gene in liver, spleen and caecum of infected chicken was seen at 9dpi, 5dpi and 9dpi respectively. This study has role in diagnostics and prognostics in the poultry industry for the detection of salmonella infections at early stages of poultry development.Keywords: biochemistry, histopathology, NRAMP, poultry, real time expression, Salmonella Typhimurium
Procedia PDF Downloads 332138 Using Convolutional Neural Networks to Distinguish Different Sign Language Alphanumerics
Authors: Stephen L. Green, Alexander N. Gorban, Ivan Y. Tyukin
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Within the past decade, using Convolutional Neural Networks (CNN)’s to create Deep Learning systems capable of translating Sign Language into text has been a breakthrough in breaking the communication barrier for deaf-mute people. Conventional research on this subject has been concerned with training the network to recognize the fingerspelling gestures of a given language and produce their corresponding alphanumerics. One of the problems with the current developing technology is that images are scarce, with little variations in the gestures being presented to the recognition program, often skewed towards single skin tones and hand sizes that makes a percentage of the population’s fingerspelling harder to detect. Along with this, current gesture detection programs are only trained on one finger spelling language despite there being one hundred and forty-two known variants so far. All of this presents a limitation for traditional exploitation for the state of current technologies such as CNN’s, due to their large number of required parameters. This work aims to present a technology that aims to resolve this issue by combining a pretrained legacy AI system for a generic object recognition task with a corrector method to uptrain the legacy network. This is a computationally efficient procedure that does not require large volumes of data even when covering a broad range of sign languages such as American Sign Language, British Sign Language and Chinese Sign Language (Pinyin). Implementing recent results on method concentration, namely the stochastic separation theorem, an AI system is supposed as an operate mapping an input present in the set of images u ∈ U to an output that exists in a set of predicted class labels q ∈ Q of the alphanumeric that q represents and the language it comes from. These inputs and outputs, along with the interval variables z ∈ Z represent the system’s current state which implies a mapping that assigns an element x ∈ ℝⁿ to the triple (u, z, q). As all xi are i.i.d vectors drawn from a product mean distribution, over a period of time the AI generates a large set of measurements xi called S that are grouped into two categories: the correct predictions M and the incorrect predictions Y. Once the network has made its predictions, a corrector can then be applied through centering S and Y by subtracting their means. The data is then regularized by applying the Kaiser rule to the resulting eigenmatrix and then whitened before being split into pairwise, positively correlated clusters. Each of these clusters produces a unique hyperplane and if any element x falls outside the region bounded by these lines then it is reported as an error. As a result of this methodology, a self-correcting recognition process is created that can identify fingerspelling from a variety of sign language and successfully identify the corresponding alphanumeric and what language the gesture originates from which no other neural network has been able to replicate.Keywords: convolutional neural networks, deep learning, shallow correctors, sign language
Procedia PDF Downloads 100137 The Use of the TRIGRS Model and Geophysics Methodologies to Identify Landslides Susceptible Areas: Case Study of Campos do Jordao-SP, Brazil
Authors: Tehrrie Konig, Cassiano Bortolozo, Daniel Metodiev, Rodolfo Mendes, Marcio Andrade, Marcio Moraes
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Gravitational mass movements are recurrent events in Brazil, usually triggered by intense rainfall. When these events occur in urban areas, they end up becoming disasters due to the economic damage, social impact, and loss of human life. To identify the landslide-susceptible areas, it is important to know the geotechnical parameters of the soil, such as cohesion, internal friction angle, unit weight, hydraulic conductivity, and hydraulic diffusivity. The measurement of these parameters is made by collecting soil samples to analyze in the laboratory and by using geophysical methodologies, such as Vertical Electrical Survey (VES). The geophysical surveys analyze the soil properties with minimal impact in its initial structure. Statistical analysis and mathematical models of physical basis are used to model and calculate the Factor of Safety for steep slope areas. In general, such mathematical models work from the combination of slope stability models and hydrological models. One example is the mathematical model TRIGRS (Transient Rainfall Infiltration and Grid-based Regional Slope- Stability Model) which calculates the variation of the Factor of Safety of a determined study area. The model relies on changes in pore-pressure and soil moisture during a rainfall event. TRIGRS was written in the Fortran programming language and associates the hydrological model, which is based on the Richards Equation, with the stability model based on the principle of equilibrium limit. Therefore, the aims of this work are modeling the slope stability of Campos do Jordão with TRIGRS, using geotechnical and geophysical methodologies to acquire the soil properties. The study area is located at southern-east of Sao Paulo State in the Mantiqueira Mountains and has a historic landslide register. During the fieldwork, soil samples were collected, and the VES method applied. These procedures provide the soil properties, which were used as input data in the TRIGRS model. The hydrological data (infiltration rate and initial water table height) and rainfall duration and intensity, were acquired from the eight rain gauges installed by Cemaden in the study area. A very high spatial resolution digital terrain model was used to identify the slopes declivity. The analyzed period is from March 6th to March 8th of 2017. As results, the TRIGRS model calculates the variation of the Factor of Safety within a 72-hour period in which two heavy rainfall events stroke the area and six landslides were registered. After each rainfall, the Factor of Safety declined, as expected. The landslides happened in areas identified by the model with low values of Factor of Safety, proving its efficiency on the identification of landslides susceptible areas. This study presents a critical threshold for landslides, in which an accumulated rainfall higher than 80mm/m² in 72 hours might trigger landslides in urban and natural slopes. The geotechnical and geophysics methods are shown to be very useful to identify the soil properties and provide the geological characteristics of the area. Therefore, the combine geotechnical and geophysical methods for soil characterization and the modeling of landslides susceptible areas with TRIGRS are useful for urban planning. Furthermore, early warning systems can be developed by combining the TRIGRS model and weather forecast, to prevent disasters in urban slopes.Keywords: landslides, susceptibility, TRIGRS, vertical electrical survey
Procedia PDF Downloads 173136 Particle Observation in Secondary School Using a Student-Built Instrument: Design-Based Research on a STEM Sequence about Particle Physics
Authors: J.Pozuelo-Muñoz, E. Cascarosa-Salillas, C. Rodríguez-Casals, A. de Echave, E. Terrado-Sieso
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This study focuses on the development, implementation, and evaluation of an instructional sequence aimed at 16–17-year-old students, involving the design and use of a cloud chamber—a device that allows observation of subatomic particles. The research addresses the limited presence of particle physics in Spanish secondary and high school curricula, a gap that restricts students' learning of advanced physics concepts and diminishes engagement with complex scientific topics. The primary goal of this project is to introduce particle physics in the classroom through a practical, interdisciplinary methodology that promotes autonomous learning and critical thinking. The methodology is framed within Design-Based Research (DBR), an approach that enables iterative and pragmatic development of educational resources. The research proceeded in several phases, beginning with the design of an experimental teaching sequence, followed by its implementation in high school classrooms. This sequence was evaluated, redesigned, and reimplemented with the aim of enhancing students’ understanding and skills related to designing and using particle detection instruments. The instructional sequence was divided into four stages: introduction to the activity, research and design of cloud chamber prototypes, observation of particle tracks, and analysis of collected data. In the initial stage, students were introduced to the fundamentals of the activity and provided with bibliographic resources to conduct autonomous research on cloud chamber functioning principles. During the design stage, students sourced materials and constructed their own prototypes, stimulating creativity and understanding of physics concepts like thermodynamics and material properties. The third stage focused on observing subatomic particles, where students recorded and analyzed the tracks generated in their chambers. Finally, critical reflection was encouraged regarding the instrument's operation and the nature of the particles observed. The results show that designing the cloud chamber motivates students and actively engages them in the learning process. Additionally, the use of this device introduces advanced scientific topics beyond particle physics, promoting a broader understanding of science. The study’s conclusions emphasize the need to provide students with ample time and space to thoroughly understand the role of materials and physical conditions in the functioning of their prototypes and to encourage critical analysis of the obtained data. This project not only highlights the importance of interdisciplinarity in science education but also provides a practical framework for teachers to adapt complex concepts for educational contexts where these topics are often absent.Keywords: cloud chamber, particle physics, secondary education, instructional design, design-based research, STEM
Procedia PDF Downloads 13135 Tangible Losses, Intangible Traumas: Re-envisioning Recovery Following the Lytton Creek Fire 2021 through Place Attachment Lens
Authors: Tugba Altin
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In an era marked by pronounced climate change consequences, communities are observed to confront traumatic events that yield both tangible and intangible repercussions. Such events not only cause discernible damage to the landscape but also deeply affect the intangible aspects, including emotional distress and disruptions to cultural landscapes. The Lytton Creek Fire of 2021 serves as a case in point. Beyond the visible destruction, the less overt but profoundly impactful disturbance to place attachment (PA) is scrutinized. PA, representing the emotional and cognitive bonds individuals establish with their environments, is crucial for understanding how such events impact cultural identity and connection to the land. The study underscores the significance of addressing both tangible and intangible traumas for holistic community recovery. As communities renegotiate their affiliations with altered environments, the cultural landscape emerges as instrumental in shaping place-based identities. This renewed understanding is pivotal for reshaping adaptation planning. The research advocates for adaptation strategies rooted in the lived experiences and testimonies of the affected populations. By incorporating both the tangible and intangible facets of trauma, planning efforts are suggested to be more culturally attuned and emotionally insightful, fostering true resonance with the affected communities. Through such a comprehensive lens, this study contributes enriching the climate change discourse, emphasizing the intertwined nature of tangible recovery and the imperative of emotional and cultural healing after environmental disasters. Following the pronounced aftermath of the Lytton Creek Fire in 2021, research aims to deeply understand its impact on place attachment (PA), encompassing the emotional and cognitive bonds individuals form with their environments. The interpretive phenomenological approach, enriched by a hermeneutic framework, is adopted, emphasizing the experiences of the Lytton community and co-researchers. Phenomenology informed the understanding of 'place' as the focal point of attachment, providing insights into its formation and evolution after traumatic events. Data collection departs from conventional methods. Instead of traditional interviews, walking audio sessions and photo elicitation methods are utilized. These allow co-researchers to immerse themselves in the environment, re-experience, and articulate memories and feelings in real-time. Walking audio facilitates reflections on spatial narratives post-trauma, while photo voices captured intangible emotions, enabling the visualization of place-based experiences. The analysis is collaborative, ensuring the co-researchers' experiences and interpretations are central. Emphasizing their agency in knowledge production, the process is rigorous, facilitated by the harmonious blend of interpretive phenomenology and hermeneutic insights. The findings underscore the need for adaptation and recovery efforts to address emotional traumas alongside tangible damages. By exploring PA post-disaster, the research not only fills a significant gap but advocates for an inclusive approach to community recovery. Furthermore, the participatory methodologies employed challenge traditional research paradigms, heralding potential shifts in qualitative research norms.Keywords: wildfire recovery, place attachment, trauma recovery, cultural landscape, visual methodologies
Procedia PDF Downloads 91134 An Evidence-Based Laboratory Medicine (EBLM) Test to Help Doctors in the Assessment of the Pancreatic Endocrine Function
Authors: Sergio J. Calleja, Adria Roca, José D. Santotoribio
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Pancreatic endocrine diseases include pathologies like insulin resistance (IR), prediabetes, and type 2 diabetes mellitus (DM2). Some of them are highly prevalent in the U.S.—40% of U.S. adults have IR, 38% of U.S. adults have prediabetes, and 12% of U.S. adults have DM2—, as reported by the National Center for Biotechnology Information (NCBI). Building upon this imperative, the objective of the present study was to develop a non-invasive test for the assessment of the patient’s pancreatic endocrine function and to evaluate its accuracy in detecting various pancreatic endocrine diseases, such as IR, prediabetes, and DM2. This approach to a routine blood and urine test is based around serum and urine biomarkers. It is made by the combination of several independent public algorithms, such as the Adult Treatment Panel III (ATP-III), triglycerides and glucose (TyG) index, homeostasis model assessment-insulin resistance (HOMA-IR), HOMA-2, and the quantitative insulin-sensitivity check index (QUICKI). Additionally, it incorporates essential measurements such as the creatinine clearance, estimated glomerular filtration rate (eGFR), urine albumin-to-creatinine ratio (ACR), and urinalysis, which are helpful to achieve a full image of the patient’s pancreatic endocrine disease. To evaluate the estimated accuracy of this test, an iterative process was performed by a machine learning (ML) algorithm, with a training set of 9,391 patients. The sensitivity achieved was 97.98% and the specificity was 99.13%. Consequently, the area under the receiver operating characteristic (AUROC) curve, the positive predictive value (PPV), and the negative predictive value (NPV) were 92.48%, 99.12%, and 98.00%, respectively. The algorithm was validated with a randomized controlled trial (RCT) with a target sample size (n) of 314 patients. However, 50 patients were initially excluded from the study, because they had ongoing clinically diagnosed pathologies, symptoms or signs, so the n dropped to 264 patients. Then, 110 patients were excluded because they didn’t show up at the clinical facility for any of the follow-up visits—this is a critical point to improve for the upcoming RCT, since the cost of each patient is very high and for this RCT almost a third of the patients already tested were lost—, so the new n consisted of 154 patients. After that, 2 patients were excluded, because some of their laboratory parameters and/or clinical information were wrong or incorrect. Thus, a final n of 152 patients was achieved. In this validation set, the results obtained were: 100.00% sensitivity, 100.00% specificity, 100.00% AUROC, 100.00% PPV, and 100.00% NPV. These results suggest that this approach to a routine blood and urine test holds promise in providing timely and accurate diagnoses of pancreatic endocrine diseases, particularly among individuals aged 40 and above. Given the current epidemiological state of these type of diseases, these findings underscore the significance of early detection. Furthermore, they advocate for further exploration, prompting the intention to conduct a clinical trial involving 26,000 participants (from March 2025 to December 2026).Keywords: algorithm, diabetes, laboratory medicine, non-invasive
Procedia PDF Downloads 32133 A Novel Paradigm in the Management of Pancreatic Trauma
Authors: E. Tan, O. McKay, T. Clarnette T., D. Croagh
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Background: Historically with pancreatic trauma, complete disruption of the main pancreatic duct (MPD), classified as Grade IV-V by the American Association for the Surgery of Trauma (AAST), necessitated a damage-control laparotomy. This was to avoid mortality, shorten diet upgrade timeframe, and hence shorter length of stay. However, acute pancreatic resection entailed complications of pancreatic fistulas and leaks. With the advance of imaging-guided interventions, non-operative management such as percutaneous and transpapillary drainage of traumatic peripancreatic collections have been trialled favourably. The aim of this case series is to evaluate the efficacy of endoscopic ultrasound-guided (EUS) transmural drainage in managing traumatic peripancreatic collections as a less invasive alternative to traditional approaches. This study also highlights the importance of anatomical knowledge regarding peripancreatic collection’s common location in the lesser sac, the pancreas relationship to adjacent organs, and the formation of the main pancreatic duct in regards to the feasibility of therapeutic internal drainage. Methodology: A retrospective case series was conducted at a single tertiary endoscopy unit, analysing patient data over a 5-year period. Inclusion criteria outlined patients age 5 to 80-years-old, traumatic pancreatic injury of at least Grade IV and haemodynamic stability. Exclusion criteria involved previous episodes of pancreatitis or abdominal trauma. Patient demographics and clinicopathological characteristics were retrospectively collected. Results: The study identified 7 patients with traumatic pancreatic injuries that were managed from 2018-2022; age ranging from 5 to 34 years old, with majority being female (n=5). Majority of the mechanisms of trauma were a handlebar injury (n=4). Diagnosis was confirmed with an elevated lipase and computerized tomotography (CT) confirmation of proximal pancreatic transection with MPD disruption. All patients sustained an isolated single organ grade IV pancreatic injury, except case 4 and 5 with other intra-abdominal visceral Grade 1 injuries. 6 patients underwent early ERCP-guided transpapillary drainage with 1 being unsuccessful for pancreatic duct stent insertion (case 1) and 1 complication of stent migration (case 2). Surveillance imaging post ERCP showed the stents were unable to bridge the disrupted duct and development of symptomatic collections with an average size of 9.9cm. Hence, all patients proceeded to EUS-guided transmural drainage, with 2/7 patients requiring repeat drainages (case 6 and 7). Majority (n=6) had a cystogastrostomy, whilst 1 (case 6) had a cystoenterostomy due to feasibility of the peripancreatic collection being adjacent to duodenum rather than stomach. However, case 6 subsequently required repeat EUS-guided drainage with cystogastrostomy for ongoing collections. Hence all patients avoided initial laparotomy with an average index length of stay of 11.7 days. Successful transmural drainage was demonstrated, with no long-term complications of pancreatic insufficiency; except for 1 patient requiring a distal pancreatectomy at 2 year follow-up due to chronic pain. Conclusion: The early results of this series support EUS-guided transmural drainage as a viable management option for traumatic peripancreatic collections, showcasing successful outcomes, minimal complications, and long-term efficacy in avoiding surgical interventions. More studies are required before the adoption of this procedure as a less invasive and complication-prone management approach for traumatic peripancreatic collections.Keywords: endoscopic ultrasound, cystogastrostomy, pancreatic trauma, traumatic peripancreatic collection, transmural drainage
Procedia PDF Downloads 47132 The Role of Intraluminal Endoscopy in the Diagnosis and Treatment of Fluid Collections in Patients With Acute Pancreatitis
Authors: A. Askerov, Y. Teterin, P. Yartcev, S. Novikov
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Introduction: Acute pancreatitis (AP) is a socially significant problem for public health and continues to be one of the most common causes of hospitalization of patients with pathology of the gastrointestinal tract. It is characterized by high mortality rates, which reaches 62-65% in infected pancreatic necrosis. Aims & Methods: The study group included 63 patients who underwent transluminal drainage (TLD) fluid collection (FC). All patients were performed transabdominal ultrasound, computer tomography of the abdominal cavity and retroperitoneal organs and endoscopic ultrasound (EUS) of the pancreatobiliary zone. The EUS was used as a final diagnostic method to determine the characteristics of FC. The indications for TLD were: the distance between the wall of the hollow organ and the FC was not more than 1 cm, the absence of large vessels on the puncture trajectory (more than 3 mm), and the size of the formation was more than 5 cm. When a homogeneous cavity with clear, even contours was detected, a plastic stent with rounded ends (“double pig tail”) was installed. The indication for the installation of a fully covered self-expanding stent was the detection of nonhomogeneous anechoic FC with hyperechoic inclusions and cloudy purulent contents. In patients with necrotic forms after drainage of the purulent cavity, a cystonasal drainage with a diameter of 7Fr was installed in its lumen under X-ray control to sanitize the cavity with a 0.05% aqueous solution of chlorhexidine. Endoscopic necrectomy was performed every 24-48 hours. The plastic stent was removed in 6 month, the fully covered self-expanding stent - in 1 month after the patient was discharged from the hospital. Results: Endoscopic TLD was performed in 63 patients. The FC corresponding to interstitial edematous pancreatitis was detected in 39 (62%) patients who underwent TLD with the installation of a plastic stent with rounded ends. In 24 (38%) patients with necrotic forms of FC, a fully covered self-expanding stent was placed. Communication with the ductal system of the pancreas was found in 5 (7.9%) patients. They underwent pancreaticoduodenal stenting. A complicated postoperative period was noted in 4 (6.3%) cases and was manifested by bleeding from the zone of pancreatogenic destruction. In 2 (3.1%) cases, this required angiography and endovascular embolization a. gastroduodenalis, in 1 (1.6%) case, endoscopic hemostasis was performed by filling the cavity with 4 ml of Hemoblock hemostatic solution. The combination of both methods was used in 1 (1.6%) patient. There was no evidence of recurrent bleeding in these patients. Lethal outcome occurred in 4 patients (6.3%). In 3 (4.7%) patients, the cause of death was multiple organ failure, in 1 (1.6%) - severe nosocomial pneumonia that developed on the 32nd day after drainage. Conclusions: 1. EUS is not only the most important method for diagnosing FC in AP, but also allows you to determine further tactics for their intraluminal drainage.2. Endoscopic intraluminal drainage of fluid zones in 45.8% of cases is the final minimally invasive method of surgical treatment of large-focal pancreatic necrosis. Disclosure: Nothing to disclose.Keywords: acute pancreatitis, fluid collection, endoscopy surgery, necrectomy, transluminal drainage
Procedia PDF Downloads 109131 Synthesis of Carbon Nanotubes from Coconut Oil and Fabrication of a Non Enzymatic Cholesterol Biosensor
Authors: Mitali Saha, Soma Das
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The fabrication of nanoscale materials for use in chemical sensing, biosensing and biological analyses has proven a promising avenue in the last few years. Cholesterol has aroused considerable interest in recent years on account of its being an important parameter in clinical diagnosis. There is a strong positive correlation between high serum cholesterol level and arteriosclerosis, hypertension, and myocardial infarction. Enzyme-based electrochemical biosensors have shown high selectivity and excellent sensitivity, but the enzyme is easily denatured during its immobilization procedure and its activity is also affected by temperature, pH, and toxic chemicals. Besides, the reproducibility of enzyme-based sensors is not very good which further restrict the application of cholesterol biosensor. It has been demonstrated that carbon nanotubes could promote electron transfer with various redox active proteins, ranging from cytochrome c to glucose oxidase with a deeply embedded redox center. In continuation of our earlier work on the synthesis and applications of carbon and metal based nanoparticles, we have reported here the synthesis of carbon nanotubes (CCNT) by burning coconut oil under insufficient flow of air using an oil lamp. The soot was collected from the top portion of the flame, where the temperature was around 6500C which was purified, functionalized and then characterized by SEM, p-XRD and Raman spectroscopy. The SEM micrographs showed the formation of tubular structure of CCNT having diameter below 100 nm. The XRD pattern indicated the presence of two predominant peaks at 25.20 and 43.80, which corresponded to (002) and (100) planes of CCNT respectively. The Raman spectrum (514 nm excitation) showed the presence of 1600 cm-1 (G-band) related to the vibration of sp2-bonded carbon and at 1350 cm-1 (D-band) responsible for the vibrations of sp3-bonded carbon. A nonenzymatic cholesterol biosensor was then fabricated on an insulating Teflon material containing three silver wires at the surface, covered by CCNT, obtained from coconut oil. Here, CCNTs worked as working as well as counter electrodes whereas reference electrode and electric contacts were made of silver. The dimensions of the electrode was 3.5 cm×1.0 cm×0.5 cm (length× width × height) and it is ideal for working with 50 µL volume like the standard screen printed electrodes. The voltammetric behavior of cholesterol at CCNT electrode was investigated by cyclic voltammeter and differential pulse voltammeter using 0.001 M H2SO4 as electrolyte. The influence of the experimental parameters on the peak currents of cholesterol like pH, accumulation time, and scan rates were optimized. Under optimum conditions, the peak current was found to be linear in the cholesterol concentration range from 1 µM to 50 µM with a sensitivity of ~15.31 μAμM−1cm−2 with lower detection limit of 0.017 µM and response time of about 6s. The long-term storage stability of the sensor was tested for 30 days and the current response was found to be ~85% of its initial response after 30 days.Keywords: coconut oil, CCNT, cholesterol, biosensor
Procedia PDF Downloads 282130 Methodology for Risk Assessment of Nitrosamine Drug Substance Related Impurities in Glipizide Antidiabetic Formulations
Authors: Ravisinh Solanki, Ravi Patel, Chhaganbhai Patel
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Purpose: The purpose of this study is to develop a methodology for the risk assessment and evaluation of nitrosamine impurities in Glipizide antidiabetic formulations. Nitroso compounds, including nitrosamines, have emerged as significant concerns in drug products, as highlighted by the ICH M7 guidelines. This study aims to identify known and potential sources of nitrosamine impurities that may contaminate Glipizide formulations and assess their presence. By determining observed or predicted levels of these impurities and comparing them with regulatory guidance, this research will contribute to ensuring the safety and quality of combination antidiabetic drug products on the market. Factors contributing to the presence of genotoxic nitrosamine contaminants in glipizide medications, such as secondary and tertiary amines, and nitroso group-complex forming molecules, will be investigated. Additionally, conditions necessary for nitrosamine formation, including the presence of nitrosating agents, and acidic environments, will be examined to enhance understanding and mitigation strategies. Method: The methodology for the study involves the implementation of the N-Nitroso Acid Precursor (NAP) test, as recommended by the WHO in 1978 and detailed in the 1980 International Agency for Research on Cancer monograph. Individual glass vials containing equivalent to 10mM quantities of Glipizide is prepared. These compounds are dissolved in an acidic environment and supplemented with 40 mM NaNO2. The resulting solutions are maintained at a temperature of 37°C for a duration of 4 hours. For the analysis of the samples, an HPLC method is employed for fit-for-purpose separation. LC resolution is achieved using a step gradient on an Agilent Eclipse Plus C18 column (4.6 X 100 mm, 3.5µ). Mobile phases A and B consist of 0.1% v/v formic acid in water and acetonitrile, respectively, following a gradient mode program. The flow rate is set at 0.6 mL/min, and the column compartment temperature is maintained at 35°C. Detection is performed using a PDA detector within the wavelength range of 190-400 nm. To determine the exact mass of formed nitrosamine drug substance related impurities (NDSRIs), the HPLC method is transferred to LC-TQ-MS/MS with the same mobile phase composition and gradient program. The injection volume is set at 5 µL, and MS analysis is conducted in Electrospray Ionization (ESI) mode within the mass range of 100−1000 Daltons. Results: The samples of NAP test were prepared according to the protocol. The samples were analyzed using HPLC and LC-TQ-MS/MS identify possible NDSRIs generated in different formulations of glipizide. It was found that the NAP test generated a various NDSRIs. The new finding, which has not been reported yet, discovered contamination of Glipizide. These NDSRIs are categorised based on the predicted carcinogenic potency and recommended its acceptable intact in medicines. The analytical method was found specific and reproducible.Keywords: NDSRI, nitrosamine impurities, antidiabetic, glipizide, LC-MS/MS
Procedia PDF Downloads 33129 Rationally Designed Dual PARP-HDAC Inhibitor Elicits Striking Anti-leukemic Effects
Authors: Amandeep Thakur, Yi-Hsuan Chu, Chun-Hsu Pan, Kunal Nepali
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The transfer of ADP-ribose residues onto target substrates from nicotinamide adenine dinucleotide (NAD) (PARylation) is catalyzed by Poly (ADP-ribose) polymerases (PARPs). Amongst the PARP family members, the DNA damage response in cancer is majorly regulated by PARP1 and PARP2. The blockade of DNA repair by PARP inhibitors leads to the progression of DNA single-strand breaks (induced by some triggering factors) to double-strand breaks. Notably, PARP inhibitors are remarkably effective in cancers with defective homologous recombination repair (HRR). In particular, cancer cells with BRCA mutations are responsive to therapy with PARP inhibitors. The aforementioned requirement for PARP inhibitors to be effective confers a narrow activity spectrum to PARP inhibitors, which hinders their clinical applicability. Thus, the quest to expand the application horizons of PARP inhibitors beyond BRCA mutations is the need of the hour. Literature precedents reveal that HDAC inhibition induces BRCAness in cancer cells and can broaden the therapeutic scope of PARP inhibitors. Driven by such disclosures, dual inhibitors targeting both PARP and HDAC enzymes were designed by our research group to extend the efficacy of PARP inhibitors beyond BRCA-mutated cancers to cancers with induced BRCAness. The design strategy involved the installation of Veliparib, an investigational PARP inhibitor, as a surface recognition part in the HDAC inhibitor pharmacophore model. The chemical architecture of veliparib was deemed appropriate as a starting point for the generation of dual inhibitors by virtue of its size and structural flexibility. A validatory docking study was conducted at the outset to predict the binding mode of the designed dual modulatory chemical architectures. Subsequently, the designed chemical architectures were synthesized via a multistep synthetic route and evaluated for antitumor efficacy. Delightfully, one compound manifested impressive anti-leukemic effects (HL-60 cell lines) mediated via dual inhibition of PARP and class I HDACs. The outcome of the western blot analysis revealed that the compound could downregulate the expression levels of PARP1 and PARP2 and the HDAC isoforms (HDAC1, 2, and 3). Also, the dual PARP-HDAC inhibitor upregulated the protein expression of the acetyl histone H3, confirming its abrogation potential for class I HDACs. In addition, the dual modulator could arrest the cell cycle at the G0/G1 phase and induce autophagy. Further, polymer-based nanoformulation of the dual inhibitor was furnished to afford targeted delivery of the dual inhibitor at the cancer site. Transmission electron microscopy (TEM) results indicate that the nanoparticles were monodispersed and spherical. Moreover, the polymeric nanoformulation exhibited an appropriate particle size. Delightfully, pH-sensitive behavior was manifested by the polymeric nanoformulation that led to selective antitumor effects towards the HL-60 cell lines. In light of the magnificent anti-leukemic profile of the identified dual PARP-HDAC inhibitor, in-vivo studies (pharmacokinetics and pharmacodynamics) are currently being conducted. Notably, the optimistic findings of the aforementioned study have spurred our research group to initiate several medicinal chemistry campaigns to create bifunctional small molecule inhibitors addressing PARP as the primary target.Keywords: PARP inhibitors, HDAC inhibitors, BRCA mutations, leukemia
Procedia PDF Downloads 23128 Edge Enhancement Visual Methodology for Fat Amount and Distribution Assessment in Dry-Cured Ham Slices
Authors: Silvia Grassi, Stefano Schiavon, Ernestina Casiraghi, Cristina Alamprese
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Dry-cured ham is an uncooked meat product particularly appreciated for its peculiar sensory traits among which lipid component plays a key role in defining quality and, consequently, consumers’ acceptability. Usually, fat content and distribution are chemically determined by expensive, time-consuming, and destructive analyses. Moreover, different sensory techniques are applied to assess product conformity to desired standards. In this context, visual systems are getting a foothold in the meat market envisioning more reliable and time-saving assessment of food quality traits. The present work aims at developing a simple but systematic and objective visual methodology to assess the fat amount of dry-cured ham slices, in terms of total, intermuscular and intramuscular fractions. To the aim, 160 slices from 80 PDO dry-cured hams were evaluated by digital image analysis and Soxhlet extraction. RGB images were captured by a flatbed scanner, converted in grey-scale images, and segmented based on intensity histograms as well as on a multi-stage algorithm aimed at edge enhancement. The latter was performed applying the Canny algorithm, which consists of image noise reduction, calculation of the intensity gradient for each image, spurious response removal, actual thresholding on corrected images, and confirmation of strong edge boundaries. The approach allowed for the automatic calculation of total, intermuscular and intramuscular fat fractions as percentages of the total slice area. Linear regression models were run to estimate the relationships between the image analysis results and the chemical data, thus allowing for the prediction of the total, intermuscular and intramuscular fat content by the dry-cured ham images. The goodness of fit of the obtained models was confirmed in terms of coefficient of determination (R²), hypothesis testing and pattern of residuals. Good regression models have been found being 0.73, 0.82, and 0.73 the R2 values for the total fat, the sum of intermuscular and intramuscular fat and the intermuscular fraction, respectively. In conclusion, the edge enhancement visual procedure brought to a good fat segmentation making the simple visual approach for the quantification of the different fat fractions in dry-cured ham slices sufficiently simple, accurate and precise. The presented image analysis approach steers towards the development of instruments that can overcome destructive, tedious and time-consuming chemical determinations. As future perspectives, the results of the proposed image analysis methodology will be compared with those of sensory tests in order to develop a fast grading method of dry-cured hams based on fat distribution. Therefore, the system will be able not only to predict the actual fat content but it will also reflect the visual appearance of samples as perceived by consumers.Keywords: dry-cured ham, edge detection algorithm, fat content, image analysis
Procedia PDF Downloads 176127 Impact of Elevated Temperature on Spot Blotch Development in Wheat and Induction of Resistance by Plant Growth Promoting Rhizobacteria
Authors: Jayanwita Sarkar, Usha Chakraborty, Bishwanath Chakraborty
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Plants are constantly interacting with various abiotic and biotic stresses. In changing climate scenario plants are continuously modifying physiological processes to adapt to changing environmental conditions which profoundly affect plant-pathogen interactions. Spot blotch in wheat is a fast-rising disease in the warmer plains of South Asia where the rise in minimum average temperature over most of the year already affecting wheat production. Hence, the study was undertaken to explore the role of elevated temperature in spot blotch disease development and modulation of antioxidative responses by plant growth promoting rhizobacteria (PGPR) for biocontrol of spot blotch at high temperature. Elevated temperature significantly increases the susceptibility of wheat plants to spot blotch causing pathogen Bipolaris sorokiniana. Two PGPR Bacillus safensis (W10) and Ochrobactrum pseudogrignonense (IP8) isolated from wheat (Triticum aestivum L.) and blady grass (Imperata cylindrical L.) rhizophere respectively, showing in vitro antagonistic activity against Bipolaris sorokiniana were tested for growth promotion and induction of resistance against spot blotch in wheat. GC-MS analysis showed that Bacillus safensis (W10) and Ochrobactrum pseudogrignonense (IP8) produced antifungal and antimicrobial compounds in culture. Seed priming with these two bacteria significantly increase growth, modulate antioxidative signaling and induce resistance and eventually reduce disease incidence in wheat plants at optimum as well as elevated temperature which was further confirmed by indirect immunofluorescence assay using polyclonal antibody raised against Bipolaris sorokiniana. Application of the PGPR led to enhancement in activities of plant defense enzymes- phenylalanine ammonia lyase, peroxidase, chitinase and β-1,3 glucanase in infected leaves. Immunolocalization of chitinase and β-1,3 glucanase in PGPR primed and pathogen inoculated leaf tissue was further confirmed by transmission electron microscopy using PAb of chitinase, β-1,3 glucanase and gold labelled conjugates. Activity of ascorbate-glutathione redox cycle related enzymes such as ascorbate peroxidase, superoxide dismutase and glutathione reductase along with antioxidants such as carotenoids, glutathione and ascorbate and osmolytes like proline and glycine betain accumulation were also increased during disease development in PGPR primed plant in comparison to unprimed plants at high temperature. Real-time PCR analysis revealed enhanced expression of defense genes- chalcone synthase and phenyl alanineammonia lyase. Over expression of heat shock proteins like HSP 70, small HSP 26.3 and heat shock factor HsfA3 in PGPR primed plants effectively protect plants against spot blotch infection at elevated temperature as compared with control plants. Our results revealed dynamic biochemical cross talk between elevated temperature and spot blotch disease development and furthermore highlight PGPR mediated array of antioxidative and molecular alterations responsible for induction of resistance against spot blotch disease at elevated temperature which seems to be associated with up-regulation of defense genes, heat shock proteins and heat shock factors, less ROS production, membrane damage, increased expression of redox enzymes and accumulation of osmolytes and antioxidants.Keywords: antioxidative enzymes, defense enzymes, elevated temperature, heat shock proteins, PGPR, Real-Time PCR, spot blotch, wheat
Procedia PDF Downloads 171126 Management of Non-Revenue Municipal Water
Authors: Habib Muhammetoglu, I. Ethem Karadirek, Selami Kara, Ayse Muhammetoglu
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The problem of non-revenue water (NRW) from municipal water distribution networks is common in many countries such as Turkey, where the average yearly water losses are around 50% . Water losses can be divided into two major types namely: 1) Real or physical water losses, and 2) Apparent or commercial water losses. Total water losses in Antalya city, Turkey is around 45%. Methods: A research study was conducted to develop appropriate methodologies to reduce NRW. A pilot study area of about 60 thousands inhabitants was chosen to apply the study. The pilot study area has a supervisory control and data acquisition (SCADA) system for the monitoring and control of many water quantity and quality parameters at the groundwater drinking wells, pumping stations, distribution reservoirs, and along the water mains. The pilot study area was divided into 18 District Metered Areas (DMAs) with different number of service connections that ranged between a few connections to less than 3000 connections. The flow rate and water pressure to each DMA were on-line continuously measured by an accurate flow meter and water pressure meter that were connected to the SCADA system. Customer water meters were installed to all billed and unbilled water users. The monthly water consumption as given by the water meters were recorded regularly. Water balance was carried out for each DMA using the well-know standard IWA approach. There were considerable variations in the water losses percentages and the components of the water losses among the DMAs of the pilot study area. Old Class B customer water meters at one DMA were replaced by more accurate new Class C water meters. Hydraulic modelling using the US-EPA EPANET model was carried out in the pilot study area for the prediction of water pressure variations at each DMA. The data sets required to calibrate and verify the hydraulic model were supplied by the SCADA system. It was noticed that a number of the DMAs exhibited high water pressure values. Therefore, pressure reducing valves (PRV) with constant head were installed to reduce the pressure up to a suitable level that was determined by the hydraulic model. On the other hand, the hydraulic model revealed that the water pressure at the other DMAs cannot be reduced when complying with the minimum pressure requirement (3 bars) as stated by the related standards. Results: Physical water losses were reduced considerably as a result of just reducing water pressure. Further physical water losses reduction was achieved by applying acoustic methods. The results of the water balances helped in identifying the DMAs that have considerable physical losses. Many bursts were detected especially in the DMAs that have high physical water losses. The SCADA system was very useful to assess the efficiency level of this method and to check the quality of repairs. Regarding apparent water losses reduction, changing the customer water meters resulted in increasing water revenue by more than 20%. Conclusions: DMA, SCADA, modelling, pressure management, leakage detection and accurate customer water meters are efficient for NRW.Keywords: NRW, water losses, pressure management, SCADA, apparent water losses, urban water distribution networks
Procedia PDF Downloads 405125 Investigating the Neural Heterogeneity of Developmental Dyscalculia
Authors: Fengjuan Wang, Azilawati Jamaludin
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Developmental Dyscalculia (DD) is defined as a particular learning difficulty with continuous challenges in learning requisite math skills that cannot be explained by intellectual disability or educational deprivation. Recent studies have increasingly recognized that DD is a heterogeneous, instead of monolithic, learning disorder with not only cognitive and behavioral deficits but so too neural dysfunction. In recent years, neuroimaging studies employed group comparison to explore the neural underpinnings of DD, which contradicted the heterogenous nature of DD and may obfuscate critical individual differences. This research aimed to investigate the neural heterogeneity of DD using case studies with functional near-infrared spectroscopy (fNIRS). A total of 54 aged 6-7 years old of children participated in this study, comprising two comprehensive cognitive assessments, an 8-minute resting state, and an 8-minute one-digit addition task. Nine children met the criteria of DD and scored at or below 85 (i.e., the 16th percentile) on the Mathematics or Math Fluency subtest of the Wechsler Individual Achievement Test, Third Edition (WIAT-III) (both subtest scores were 90 and below). The remaining 45 children formed the typically developing (TD) group. Resting-state data and brain activation in the inferior frontal gyrus (IFG), superior frontal gyrus (SFG), and intraparietal sulcus (IPS) were collected for comparison between each case and the TD group. Graph theory was used to analyze the brain network under the resting state. This theory represents the brain network as a set of nodes--brain regions—and edges—pairwise interactions across areas to reveal the architectural organizations of the nervous network. Next, a single-case methodology developed by Crawford et al. in 2010 was used to compare each case’s brain network indicators and brain activation against 45 TD children’s average data. Results showed that three out of the nine DD children displayed significant deviation from TD children’s brain indicators. Case 1 had inefficient nodal network properties. Case 2 showed inefficient brain network properties and weaker activation in the IFG and IPS areas. Case 3 displayed inefficient brain network properties with no differences in activation patterns. As a rise above, the present study was able to distill differences in architectural organizations and brain activation of DD vis-à-vis TD children using fNIRS and single-case methodology. Although DD is regarded as a heterogeneous learning difficulty, it is noted that all three cases showed lower nodal efficiency in the brain network, which may be one of the neural sources of DD. Importantly, although the current “brain norm” established for the 45 children is tentative, the results from this study provide insights not only for future work in “developmental brain norm” with reliable brain indicators but so too the viability of single-case methodology, which could be used to detect differential brain indicators of DD children for early detection and interventions.Keywords: brain activation, brain network, case study, developmental dyscalculia, functional near-infrared spectroscopy, graph theory, neural heterogeneity
Procedia PDF Downloads 53124 Fold and Thrust Belts Seismic Imaging and Interpretation
Authors: Sunjay
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Plate tectonics is of very great significance as it represents the spatial relationships of volcanic rock suites at plate margins, the distribution in space and time of the conditions of different metamorphic facies, the scheme of deformation in mountain belts, or orogens, and the association of different types of economic deposit. Orogenic belts are characterized by extensive thrust faulting, movements along large strike-slip fault zones, and extensional deformation that occur deep within continental interiors. Within oceanic areas there also are regions of crustal extension and accretion in the backarc basins that are located on the landward sides of many destructive plate margins.Collisional orogens develop where a continent or island arc collides with a continental margin as a result of subduction. collisional and noncollisional orogens can be explained by differences in the strength and rheology of the continental lithosphere and by processes that influence these properties during orogenesis.Seismic Imaging Difficulties-In triangle zones, several factors reduce the effectiveness of seismic methods. The topography in the central part of the triangle zone is usually rugged and is associated with near-surface velocity inversions which degrade the quality of the seismic image. These characteristics lead to low signal-to-noise ratio, inadequate penetration of energy through overburden, poor geophone coupling with the surface and wave scattering. Depth Seismic Imaging Techniques-Seismic processing relates to the process of altering the seismic data to suppress noise, enhancing the desired signal (higher signal-to-noise ratio) and migrating seismic events to their appropriate location in space and depth. Processing steps generally include analysis of velocities, static corrections, moveout corrections, stacking and migration. Exploration seismology Bow-tie effect -Shadow Zones-areas with no reflections (dead areas). These are called shadow zones and are common in the vicinity of faults and other discontinuous areas in the subsurface. Shadow zones result when energy from a reflector is focused on receivers that produce other traces. As a result, reflectors are not shown in their true positions. Subsurface Discontinuities-Diffractions occur at discontinuities in the subsurface such as faults and velocity discontinuities (as at “bright spot” terminations). Bow-tie effect caused by the two deep-seated synclines. Seismic imaging of thrust faults and structural damage-deepwater thrust belts, Imaging deformation in submarine thrust belts using seismic attributes,Imaging thrust and fault zones using 3D seismic image processing techniques, Balanced structural cross sections seismic interpretation pitfalls checking, The seismic pitfalls can originate due to any or all of the limitations of data acquisition, processing, interpretation of the subsurface geology,Pitfalls and limitations in seismic attribute interpretation of tectonic features, Seismic attributes are routinely used to accelerate and quantify the interpretation of tectonic features in 3D seismic data. Coherence (or variance) cubes delineate the edges of megablocks and faulted strata, curvature delineates folds and flexures, while spectral components delineate lateral changes in thickness and lithology. Carbon capture and geological storage leakage surveillance because fault behave as a seal or a conduit for hydrocarbon transportation to a trap,etc.Keywords: tectonics, seismic imaging, fold and thrust belts, seismic interpretation
Procedia PDF Downloads 70123 Howard Mold Count of Tomato Pulp Commercialized in the State of São Paulo, Brazil
Authors: M. B. Atui, A. M. Silva, M. A. M. Marciano, M. I. Fioravanti, V. A. Franco, L. B. Chasin, A. R. Ferreira, M. D. Nogueira
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Fungi attack large amount of fruits and those who have suffered an injury on the surface are more susceptible to the growth, as they have pectinolytic enzymes that destroy the edible portion forming an amorphous and soft dough. The spores can reach the plant by the wind, rain and insects and fruit may have on its surface, besides the contaminants from the fruit trees, land and water, forming a flora composed mainly of yeasts and molds. Other contamination can occur for the equipment used to harvest, for the use of boxes and contaminated water to the fruit washing, for storage in dirty places. The hyphae in tomato products indicate the use of raw materials contaminated or unsuitable hygiene conditions during processing. Although fungi are inactivated in heat processing step, its hyphae remain in the final product and search for detection and quantification is an indicator of the quality of raw material. Howard Method count of fungi mycelia in industrialized pulps evaluates the amount of decayed fruits existing in raw material. The Brazilian legislation governing processed and packaged products set the limit of 40% of positive fields in tomato pulps. The aim of this study was to evaluate the quality of the tomato pulp sold in greater São Paulo, through a monitoring during the four seasons of the year. All over 2010, 110 samples have been examined; 21 were taking in spring, 31 in summer, 31 in fall and 27 in winter, all from different lots and trademarks. Samples have been picked up in several stores located in the city of São Paulo. Howard method was used, recommended by the AOAC, 19th ed, 2011 16:19:02 technique - method 965.41. Hundred percent of the samples contained fungi mycelia. The count average of fungi mycelia per season was 23%, 28%, 8,2% and 9,9% in spring, summer, fall and winter, respectively. Regarding the spring samples of the 21 samples analyzed, 14.3% were off-limits proposed by the legislation. As for the samples of the fall and winter, all were in accordance with the legislation and the average of mycelial filament count has not exceeded 20%, which can be explained by the low temperatures during this time of the year. The acquired samples in the summer and spring showed high percentage of fungal mycelium in the final product, related to the high temperatures in these seasons. Considering that the limit of 40% of positive fields is accepted for the Brazilian Legislation (RDC nº 14/2014), 3 spring samples (14%) and 6 summer samples (19%) will be over this limit and subject to law penalties. According to gathered data, 82% of manufacturers of this product manage to keep acceptable levels of fungi mycelia in their product. In conclusion, only 9.2% samples were for the limits established by Resolution RDC. 14/2014, showing that the limit of 40% is feasible and can be used by these segment industries. The result of the filament count mycelial by Howard method is an important tool in the microscopic analysis since it measures the quality of raw material used in the production of tomato products.Keywords: fungi, howard, method, tomato, pulps
Procedia PDF Downloads 374122 Employing Remotely Sensed Soil and Vegetation Indices and Predicting by Long Short-Term Memory to Irrigation Scheduling Analysis
Authors: Elham Koohikerade, Silvio Jose Gumiere
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In this research, irrigation is highlighted as crucial for improving both the yield and quality of potatoes due to their high sensitivity to soil moisture changes. The study presents a hybrid Long Short-Term Memory (LSTM) model aimed at optimizing irrigation scheduling in potato fields in Quebec City, Canada. This model integrates model-based and satellite-derived datasets to simulate soil moisture content, addressing the limitations of field data. Developed under the guidance of the Food and Agriculture Organization (FAO), the simulation approach compensates for the lack of direct soil sensor data, enhancing the LSTM model's predictions. The model was calibrated using indices like Surface Soil Moisture (SSM), Normalized Vegetation Difference Index (NDVI), Enhanced Vegetation Index (EVI), and Normalized Multi-band Drought Index (NMDI) to effectively forecast soil moisture reductions. Understanding soil moisture and plant development is crucial for assessing drought conditions and determining irrigation needs. This study validated the spectral characteristics of vegetation and soil using ECMWF Reanalysis v5 (ERA5) and Moderate Resolution Imaging Spectrometer (MODIS) data from 2019 to 2023, collected from agricultural areas in Dolbeau and Peribonka, Quebec. Parameters such as surface volumetric soil moisture (0-7 cm), NDVI, EVI, and NMDI were extracted from these images. A regional four-year dataset of soil and vegetation moisture was developed using a machine learning approach combining model-based and satellite-based datasets. The LSTM model predicts soil moisture dynamics hourly across different locations and times, with its accuracy verified through cross-validation and comparison with existing soil moisture datasets. The model effectively captures temporal dynamics, making it valuable for applications requiring soil moisture monitoring over time, such as anomaly detection and memory analysis. By identifying typical peak soil moisture values and observing distribution shapes, irrigation can be scheduled to maintain soil moisture within Volumetric Soil Moisture (VSM) values of 0.25 to 0.30 m²/m², avoiding under and over-watering. The strong correlations between parcels suggest that a uniform irrigation strategy might be effective across multiple parcels, with adjustments based on specific parcel characteristics and historical data trends. The application of the LSTM model to predict soil moisture and vegetation indices yielded mixed results. While the model effectively captures the central tendency and temporal dynamics of soil moisture, it struggles with accurately predicting EVI, NDVI, and NMDI.Keywords: irrigation scheduling, LSTM neural network, remotely sensed indices, soil and vegetation monitoring
Procedia PDF Downloads 41121 A System for Preventing Inadvertent Exposition of Staff Present outside the Operating Theater: Description and Clinical Test
Authors: Aya Al Masri, Kamel Guerchouche, Youssef Laynaoui, Safoin Aktaou, Malorie Martin, Fouad Maaloul
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Introduction: Mobile C-arms move throughout operating rooms of the operating theater. Being designed to move between rooms, they are not equipped with relays to retrieve the exposition information and export it outside the room. Therefore, no light signaling is available outside the room to warn the X-ray emission for staff. Inadvertent exposition of staff outside the operating theater is a real problem for radiation protection. The French standard NFC 15-160 require that: (1) access to any room containing an X-ray emitting device must be controlled by a light signage so that it cannot be inadvertently crossed, and (2) setting up an emergency button to stop the X-ray emission. This study presents a system that we developed to meet these requirements and the results of its clinical test. Materials and methods: The system is composed of two communicating boxes: o The "DetectBox" is to be installed inside the operating theater. It identifies the various operation states of the C-arm by analyzing its power supply signal. The DetectBox communicates (in wireless mode) with the second box (AlertBox). o The "AlertBox" can operate in socket or battery mode and is to be installed outside the operating theater. It detects and reports the state of the C-arm by emitting a real time light signal. This latter can have three different colors: red when the C-arm is emitting X-rays, orange when it is powered on but does not emit X-rays, and green when it is powered off. The two boxes communicate on a radiofrequency link exclusively carried out in the ‘Industrial, Scientific and Medical (ISM)’ frequency bands and allows the coexistence of several on-site warning systems without communication conflicts (interference). Taking into account the complexity of performing electrical works in the operating theater (for reasons of hygiene and continuity of medical care), this system (having a size <10 cm²) works in complete safety without any intrusion in the mobile C-arm and does not require specific electrical installation work. The system is equipped with emergency button that stops X-ray emission. The system has been clinically tested. Results: The clinical test of the system shows that: it detects X-rays having both high and low energy (50 – 150 kVp), high and low photon flow (0.5 – 200 mA: even when emitted for a very short time (<1 ms)), Probability of false detection < 10-5, it operates under all acquisition modes (continuous, pulsed, fluoroscopy mode, image mode, subtraction and movie mode), it is compatible with all C-arm models and brands. We have also tested the communication between the two boxes (DetectBox and AlertBox) in several conditions: (1) Unleaded room, (2) leaded room, and (3) rooms with particular configuration (sas, great distances, concrete walls, 3 mm of lead). The result of these last tests was positive. Conclusion: This system is a reliable tool to alert the staff present outside the operating room for X-ray emission and insure their radiation protection.Keywords: Clinical test, Inadvertent staff exposition, Light signage, Operating theater
Procedia PDF Downloads 126120 TRAC: A Software Based New Track Circuit for Traffic Regulation
Authors: Jérôme de Reffye, Marc Antoni
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Following the development of the ERTMS system, we think it is interesting to develop another software-based track circuit system which would fit secondary railway lines with an easy-to-work implementation and a low sensitivity to rail-wheel impedance variations. We called this track circuit 'Track Railway by Automatic Circuits.' To be internationally implemented, this system must not have any mechanical component and must be compatible with existing track circuit systems. For example, the system is independent from the French 'Joints Isolants Collés' that isolate track sections from one another, and it is equally independent from component used in Germany called 'Counting Axles,' in French 'compteur d’essieux.' This track circuit is fully interoperable. Such universality is obtained by replacing the train detection mechanical system with a space-time filtering of train position. The various track sections are defined by the frequency of a continuous signal. The set of frequencies related to the track sections is a set of orthogonal functions in a Hilbert Space. Thus the failure probability of track sections separation is precisely calculated on the basis of signal-to-noise ratio. SNR is a function of the level of traction current conducted by rails. This is the reason why we developed a very powerful algorithm to reject noise and jamming to obtain an SNR compatible with the precision required for the track circuit and SIL 4 level. The SIL 4 level is thus reachable by an adjustment of the set of orthogonal functions. Our major contributions to railway engineering signalling science are i) Train space localization is precisely defined by a calibration system. The operation bypasses the GSM-R radio system of the ERTMS system. Moreover, the track circuit is naturally protected against radio-type jammers. After the calibration operation, the track circuit is autonomous. ii) A mathematical topology adapted to train space localization by following the train through a linear time filtering of the received signal. Track sections are numerically defined and can be modified with a software update. The system was numerically simulated, and results were beyond our expectations. We achieved a precision of one meter. Rail-ground and rail-wheel impedance sensitivity analysis gave excellent results. Results are now complete and ready to be published. This work was initialised as a research project of the French Railways developed by the Pi-Ramses Company under SNCF contract and required five years to obtain the results. This track circuit is already at Level 3 of the ERTMS system, and it will be much cheaper to implement and to work. The traffic regulation is based on variable length track sections. As the traffic growths, the maximum speed is reduced, and the track section lengths are decreasing. It is possible if the elementary track section is correctly defined for the minimum speed and if every track section is able to emit with variable frequencies.Keywords: track section, track circuits, space-time crossing, adaptive track section, automatic railway signalling
Procedia PDF Downloads 331119 Molecular Signaling Involved in the 'Benzo(a)Pyrene' Induced Germ Cell DNA Damage and Apoptosis: Possible Protection by Natural Aryl Hydrocarbon Receptor Antagonist and Anti-Tumor Agent
Authors: Kuladip Jana
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Benzo(a)pyrene [B(a)P] is an environmental toxicant present mostly in cigarette smoke and car exhaust, is an aryl hydrocarbon receptor (AhR) ligand that exerts its toxic effects on both male and female reproductive systems. In this study, the effect of B(a)P at different doses (0.1, 0.25, 0.5, 1 and 5 mg /kg body weight) was studied on male reproductive system of rat. A significant decrease in cauda epididymal sperm count and motility along with the presence of sperm head abnormalities and altered epididymal and testicular histology were documented following B(a)P treatment. B(a)P treatment resulted apoptotic sperm cells as observed by TUNEL and Annexin V-PI assay with increased ROS, altered sperm mitochondrial membrane potential (ΔΨm) with a simultaneous decrease in the activity of antioxidant enzymes and GSH status. TUNEL positive apoptotic cells also observed in testis as well as isolated germ and Leydig cells following B(a)P exposure. Western Blot analysis revealed the activation of p38MAPK, cytosolic translocation of cytochrome-c, up-regulation of Bax and inducible nitric oxide synthase (iNOS) with cleavage of PARP and down-regulation of BCl2 in testis upon B(a)P treatment. The protein and mRNA levels of testicular key steroidogenesis regulatory proteins like StAR, cytochrome P450 IIA1 (CYPIIA1), 3β HSD, 17β HSD showed a significant decrease in a dose dependent manner while an increase in the expression of cytochrome P450 1A1 (CYP1A1), Aryl hydrocarbon Receptor (AhR), active caspase- 9 and caspase- 3 following B(a)P exposure. We conclude that exposure of benzo(a)pyrene caused testicular gamatogenic and steroidogenic disorders by induction of oxidative stress, inhibition of StAR and other steroidogenic enzymes along with activation of p38MAPK and initiated caspase-3 mediated germ and Leydig cell apoptosis.The possible protective role of naturally occurring phytochemicals against B(a)P induced testicular toxicity needs immediate consideration. Curcumin and resveratrol separately were found to protect against B(a)P induced germ cell apoptosis, and their combinatorial effect was more significant. Our present study in isolated testicular germ cell population from adult male Wistar rats, highlighted their synergistic protective effect against B(a)P induced germ cell apoptosis. Curcumin-resveratrol co-treatment decreased the expression of pro-apoptotic proteins like cleaved caspase 3,8,9, cleaved PARP, Apaf1, FasL, tBid. Curcumin-resveratrol co-treatment decreased Bax/Bcl2 ratio, mitochondria to cytosolic translocation of cytochrome c and activated the survival protein Akt. Curcumin-resveratrol decreased the expression of p53 dependent apoptotic genes like Fas, FasL, Bax, Bcl2, Apaf1.Curcumin-resveratrol co-treatment thus prevented B(a)P induced germ cell apoptosis. B(a)P induced testicular ROS generation and oxidative stress were significantly ameliorated with curcumin and resveratrol. Curcumin-resveratrol co-treatment prevented B(a)P induced nuclear translocation of AhR and CYP1A1 production. The combinatorial treatment significantly inhibited B(a)P induced ERK 1/2, p38 MAPK and JNK 1/2 activation. B(a)P treatment increased the expression of p53 and its phosphorylation (p53 ser 15). Curcumin-resveratrol co-treatment significantly decreased p53 level and its phosphorylation (p53 ser 15). The study concludes that curcumin-resveratrol synergistically modulated MAPKs and p53, prevented oxidative stress, regulated the expression of pro and anti-apoptotic proteins as well as the proteins involved in B(a)P metabolism thus protected germ cells from B(a)P induced apoptosis.Keywords: benzo(a)pyrene, germ cell, apoptosis, oxidative stress, resveratrol, curcumin
Procedia PDF Downloads 260118 Improving Binding Selectivity in Molecularly Imprinted Polymers from Templates of Higher Biomolecular Weight: An Application in Cancer Targeting and Drug Delivery
Authors: Ben Otange, Wolfgang Parak, Florian Schulz, Michael Alexander Rubhausen
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The feasibility of extending the usage of molecular imprinting technique in complex biomolecules is demonstrated in this research. This technique is promising in diverse applications in areas such as drug delivery, diagnosis of diseases, catalysts, and impurities detection as well as treatment of various complications. While molecularly imprinted polymers MIP remain robust in the synthesis of molecules with remarkable binding sites that have high affinities to specific molecules of interest, extending the usage to complex biomolecules remains futile. This work reports on the successful synthesis of MIP from complex proteins: BSA, Transferrin, and MUC1. We show in this research that despite the heterogeneous binding sites and higher conformational flexibility of the chosen proteins, relying on their respective epitopes and motifs rather than the whole template produces highly sensitive and selective MIPs for specific molecular binding. Introduction: Proteins are vital in most biological processes, ranging from cell structure and structural integrity to complex functions such as transport and immunity in biological systems. Unlike other imprinting templates, proteins have heterogeneous binding sites in their complex long-chain structure, which makes their imprinting to be marred by challenges. In addressing this challenge, our attention is inclined toward the targeted delivery, which will use molecular imprinting on the particle surface so that these particles may recognize overexpressed proteins on the target cells. Our goal is thus to make surfaces of nanoparticles that specifically bind to the target cells. Results and Discussions: Using epitopes of BSA and MUC1 proteins and motifs with conserved receptors of transferrin as the respective templates for MIPs, significant improvement in the MIP sensitivity to the binding of complex protein templates was noted. Through the Fluorescence Correlation Spectroscopy FCS measurements on the size of protein corona after incubation of the synthesized nanoparticles with proteins, we noted a high affinity of MIPs to the binding of their respective complex proteins. In addition, quantitative analysis of hard corona using SDS-PAGE showed that only a specific protein was strongly bound on the respective MIPs when incubated with similar concentrations of the protein mixture. Conclusion: Our findings have shown that the merits of MIPs can be extended to complex molecules of higher biomolecular mass. As such, the unique merits of the technique, including high sensitivity and selectivity, relative ease of synthesis, production of materials with higher physical robustness, and higher stability, can be extended to more templates that were previously not suitable candidates despite their abundance and usage within the body.Keywords: molecularly imprinted polymers, specific binding, drug delivery, high biomolecular mass-templates
Procedia PDF Downloads 55117 Telomerase, a Biomarker in Oral Cancer Cell Proliferation and Tool for Its Prevention at Initial Stage
Authors: Shaista Suhail
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As cancer populations is increasing sharply, the incidence of oral squamous cell carcinoma (OSCC) has also been expected to increase. Oral carcinogenesis is a highly complex, multistep process which involves accumulation of genetic alterations that lead to the induction of proteins promoting cell growth (encoded by oncogenes), increased enzymatic (telomerase) activity promoting cancer cell proliferation. The global increase in frequency and mortality, as well as the poor prognosis of oral squamous cell carcinoma, has intensified current research efforts in the field of prevention and early detection of this disease. The advances in the understanding of the molecular basis of oral cancer should help in the identification of new markers. The study of the carcinogenic process of the oral cancer, including continued analysis of new genetic alterations, along with their temporal sequencing during initiation, promotion and progression, will allow us to identify new diagnostic and prognostic factors, which will provide a promising basis for the application of more rational and efficient treatments. Telomerase activity has been readily found in most cancer biopsies, in premalignant lesions or germ cells. Activity of telomerase is generally absent in normal tissues. It is known to be induced upon immortalization or malignant transformation of human cells such as in oral cancer cells. Maintenance of telomeres plays an essential role during transformation of precancer to malignant stage. Mammalian telomeres, a specialized nucleoprotein structures are composed of large conctamers of the guanine-rich sequence 5_-TTAGGG-3_. The roles of telomeres in regulating both stability of genome and replicative immortality seem to contribute in essential ways in cancer initiation and progression. It is concluded that activity of telomerase can be used as a biomarker for diagnosis of malignant oral cancer and a target for inactivation in chemotherapy or gene therapy. Its expression will also prove to be an important diagnostic tool as well as a novel target for cancer therapy. The activation of telomerase may be an important step in tumorgenesis which can be controlled by inactivating its activity during chemotherapy. The expression and activity of telomerase are indispensable for cancer development. There are no drugs which can effect extremely to treat oral cancers. There is a general call for new emerging drugs or methods that are highly effective towards cancer treatment, possess low toxicity, and have a minor environment impact. Some novel natural products also offer opportunities for innovation in drug discovery. Natural compounds isolated from medicinal plants, as rich sources of novel anticancer drugs, have been of increasing interest with some enzyme (telomerase) blockage property. The alarming reports of cancer cases increase the awareness amongst the clinicians and researchers pertaining to investigate newer drug with low toxicity.Keywords: oral carcinoma, telomere, telomerase, blockage
Procedia PDF Downloads 175116 Investigation of Alumina Membrane Coated Titanium Implants on Osseointegration
Authors: Pinar Erturk, Sevde Altuntas, Fatih Buyukserin
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In order to obtain an effective integration between an implant and a bone, implant surfaces should have similar properties to bone tissue surfaces. Especially mimicry of the chemical, mechanical and topographic properties of the implant to the bone is crucial for fast and effective osseointegration. Titanium-based biomaterials are more preferred in clinical use, and there are studies of coating these implants with oxide layers that have chemical/nanotopographic properties stimulating cell interactions for enhanced osseointegration. There are low success rates of current implantations, especially in craniofacial implant applications, which are large and vital zones, and the oxide layer coating increases bone-implant integration providing long-lasting implants without requiring revision surgery. Our aim in this study is to examine bone-cell behavior on titanium implants with an aluminum oxide layer (AAO) on effective osseointegration potential in the deformation of large zones with difficult spontaneous healing. In our study, aluminum layer coated titanium surfaces were anodized in sulfuric, phosphoric, and oxalic acid, which are the most common used AAO anodization electrolytes. After morphologic, chemical, and mechanical tests on AAO coated Ti substrates, viability, adhesion, and mineralization of adult bone cells on these substrates were analyzed. Besides with atomic layer deposition (ALD) as a sensitive and conformal technique, these surfaces were coated with pure alumina (5 nm); thus, cell studies were performed on ALD-coated nanoporous oxide layers with suppressed ionic content too. Lastly, in order to investigate the effect of the topography on the cell behavior, flat non-porous alumina layers on silicon wafers formed by ALD were compared with the porous ones. Cell viability ratio was similar between anodized surfaces, but pure alumina coated titanium and anodized surfaces showed a higher viability ratio compared to bare titanium and bare anodized ones. Alumina coated titanium surfaces, which anodized in phosphoric acid, showed significantly different mineralization ratios after 21 days over other bare titanium and titanium surfaces which anodized in other electrolytes. Bare titanium was the second surface that had the highest mineralization ratio. Otherwise, titanium, which is anodized in oxalic acid electrolyte, demonstrated the lowest mineralization. No significant difference was shown between bare titanium and anodized surfaces except AAO titanium surface anodized in phosphoric acid. Currently, osteogenic activities of these cells on the genetic level are investigated by quantitative real-time polymerase chain reaction (qRT-PCR) analysis results of RUNX-2, VEGF, OPG, and osteopontin genes. Also, as a result of the activities of the genes mentioned before, Western Blot will be used for protein detection. Acknowledgment: The project is supported by The Scientific and Technological Research Council of Turkey.Keywords: alumina, craniofacial implant, MG-63 cell line, osseointegration, oxalic acid, phosphoric acid, sulphuric acid, titanium
Procedia PDF Downloads 131115 Development of a Human Skin Explant Model for Drug Metabolism and Toxicity Studies
Authors: K. K. Balavenkatraman, B. Bertschi, K. Bigot, A. Grevot, A. Doelemeyer, S. D. Chibout, A. Wolf, F. Pognan, N. Manevski, O. Kretz, P. Swart, K. Litherland, J. Ashton-Chess, B. Ling, R. Wettstein, D. J. Schaefer
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Skin toxicity is poorly detected during preclinical studies, and drug-induced side effects in humans such as rashes, hyperplasia or more serious events like bullous pemphigus or toxic epidermal necrolysis represent an important hurdle for clinical development. In vitro keratinocyte-based epidermal skin models are suitable for the detection of chemical-induced irritancy, but do not recapitulate the biological complexity of full skin and fail to detect potential serious side-effects. Normal healthy skin explants may represent a valuable complementary tool, having the advantage of retaining the full skin architecture and the resident immune cell diversity. This study investigated several conditions for the maintenance of good morphological structure after several days of culture and the retention of phase II metabolism for 24 hours in skin explants in vitro. Human skin samples were collected with informed consent from patients undergoing plastic surgery and immediately transferred and processed in our laboratory by removing the underlying dermal fat. Punch biopsies of 4 mm diameter were cultured in an air-liquid interface using transwell filters. Different cultural conditions such as the effect of calcium, temperature and cultivation media were tested for a period of 14 days and explants were histologically examined after Hematoxylin and Eosin staining. Our results demonstrated that the use of Williams E Medium at 32°C maintained the physiological integrity of the skin for approximately one week. Upon prolonged incubation, the upper layers of the epidermis become thickened and some dead cells are present. Interestingly, these effects were prevented by addition of EGFR inhibitors such as Afatinib or Erlotinib. Phase II metabolism of the skin such as glucuronidation (4-methyl umbeliferone), sulfation (minoxidil), N-acetyltransferase (p-toluidene), catechol methylation (2,3-dehydroxy naphthalene), and glutathione conjugation (chlorodinitro benzene) were analyzed by using LCMS. Our results demonstrated that the human skin explants possess metabolic activity for a period of at least 24 hours for all the substrates tested. A time course for glucuronidation with 4-methyl umbeliferone was performed and a linear correlation was obtained over a period of 24 hours. Longer-term culture studies will indicate the possible evolution of such metabolic activities. In summary, these results demonstrate that human skin explants maintain a normal structure for several days in vitro and are metabolically active for at least the first 24 hours. Hence, with further characterisation, this model may be suitable for the study of drug-induced toxicity.Keywords: human skin explant, phase II metabolism, epidermal growth factor receptor, toxicity
Procedia PDF Downloads 281114 Valorization of Surveillance Data and Assessment of the Sensitivity of a Surveillance System for an Infectious Disease Using a Capture-Recapture Model
Authors: Jean-Philippe Amat, Timothée Vergne, Aymeric Hans, Bénédicte Ferry, Pascal Hendrikx, Jackie Tapprest, Barbara Dufour, Agnès Leblond
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The surveillance of infectious diseases is necessary to describe their occurrence and help the planning, implementation and evaluation of risk mitigation activities. However, the exact number of detected cases may remain unknown whether surveillance is based on serological tests because identifying seroconversion may be difficult. Moreover, incomplete detection of cases or outbreaks is a recurrent issue in the field of disease surveillance. This study addresses these two issues. Using a viral animal disease as an example (equine viral arteritis), the goals were to establish suitable rules for identifying seroconversion in order to estimate the number of cases and outbreaks detected by a surveillance system in France between 2006 and 2013, and to assess the sensitivity of this system by estimating the total number of outbreaks that occurred during this period (including unreported outbreaks) using a capture-recapture model. Data from horses which exhibited at least one positive result in serology using viral neutralization test between 2006 and 2013 were used for analysis (n=1,645). Data consisted of the annual antibody titers and the location of the subjects (towns). A consensus among multidisciplinary experts (specialists in the disease and its laboratory diagnosis, epidemiologists) was reached to consider seroconversion as a change in antibody titer from negative to at least 32 or as a three-fold or greater increase. The number of seroconversions was counted for each town and modeled using a unilist zero-truncated binomial (ZTB) capture-recapture model with R software. The binomial denominator was the number of horses tested in each infected town. Using the defined rules, 239 cases located in 177 towns (outbreaks) were identified from 2006 to 2013. Subsequently, the sensitivity of the surveillance system was estimated as the ratio of the number of detected outbreaks to the total number of outbreaks that occurred (including unreported outbreaks) estimated using the ZTB model. The total number of outbreaks was estimated at 215 (95% credible interval CrI95%: 195-249) and the surveillance sensitivity at 82% (CrI95%: 71-91). The rules proposed for identifying seroconversion may serve future research. Such rules, adjusted to the local environment, could conceivably be applied in other countries with surveillance programs dedicated to this disease. More generally, defining ad hoc algorithms for interpreting the antibody titer could be useful regarding other human and animal diseases and zoonosis when there is a lack of accurate information in the literature about the serological response in naturally infected subjects. This study shows how capture-recapture methods may help to estimate the sensitivity of an imperfect surveillance system and to valorize surveillance data. The sensitivity of the surveillance system of equine viral arteritis is relatively high and supports its relevance to prevent the disease spreading.Keywords: Bayesian inference, capture-recapture, epidemiology, equine viral arteritis, infectious disease, seroconversion, surveillance
Procedia PDF Downloads 297113 Antimicrobial Efficacy of Some Antibiotics Combinations Tested against Some Molecular Characterized Multiresistant Staphylococcus Clinical Isolates, in Egypt
Authors: Nourhan Hussein Fanaki, Hoda Mohamed Gamal El-Din Omar, Nihal Kadry Moussa, Eva Adel Edward Farid
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The resistance of staphylococci to various antibiotics has become a major concern for health care professionals. The efficacy of the combinations of selected glycopeptides (vancomycin and teicoplanin) with gentamicin or rifampicin, as well as that of gentamicin/rifampicin combination, was studied against selected pathogenic staphylococcus isolated from Egypt. The molecular distribution of genes conferring resistance to these four antibiotics was detected among tested clinical isolates. Antibiotic combinations were studied using the checkerboard technique and the time-kill assay (in both the stationary and log phases). Induction of resistance to glycopeptides in staphylococci was tried in the absence and presence of diclofenac sodium as inducer. Transmission electron microscopy was used to study the effect of glycopeptides on the ultrastructure of the cell wall of staphylococci. Attempts were made to cure gentamicin resistance plasmids and to study the transfer of these plasmids by conjugation. Trials for the transformation of the successfully isolated gentamicin resistance plasmid to competent cells were carried out. The detection of genes conferring resistance to the tested antibiotics was performed using the polymerase chain reaction. The studied antibiotic combinations proved their efficacy, especially when tested during the log phase. Induction of resistance to glycopeptides in staphylococci was more promising in presence of diclofenac sodium, compared to its absence. Transmission electron microscopy revealed the thickening of bacterial cell wall in staphylococcus clinical isolates due to the presence of tested glycopeptides. Curing of gentamicin resistance plasmids was only successful in 2 out of 9 tested isolates, with a curing rate of 1 percent for each. Both isolates, when used as donors in conjugation experiments, yielded promising conjugation frequencies ranging between 5.4 X 10-2 and 7.48 X 10-2 colony forming unit/donor cells. Plasmid isolation was only successful in one out of the two tested isolates. However, low transformation efficiency (59.7 transformants/microgram plasmid DNA) of such plasmids was obtained. Negative regulators of autolysis, such as arlR, lytR and lrgB, as well as cell-wall associated genes, such as pbp4 and/or pbp2, were detected in staphylococcus isolates with reduced susceptibility to the tested glycopeptides. Concerning rifampicin resistance genes, rpoBstaph was detected in 75 percent of the tested staphylococcus isolates. It could be concluded that in vitro studies emphasized the usefulness of the combination of vancomycin or teicoplanin with gentamicin or rifampicin, as well as that of gentamicin with rifampicin, against staphylococci showing varying resistance patterns. However, further in vivo studies are required to ensure the safety and efficacy of such combinations. Diclofenac sodium can act as an inducer of resistance to glycopeptides in staphylococci. Cell-wall thickness is a major contributor to such resistance among them. Gentamicin resistance in these strains could be chromosomally or plasmid mediated. Multiple mutations in the rpoB gene could mediate staphylococcus resistance to rifampicin.Keywords: glycopeptides, combinations, induction, diclofenac, transmission electron microscopy, polymerase chain reaction
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