Search results for: bearing defect diagnosis
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 3160

Search results for: bearing defect diagnosis

2440 A Case Report on Neonatal Conjunctivitis in Pugs

Authors: Maria L. G. Lourenco, Viviane Y. Hibaru, Keylla H. N. P. Pereira, Fabiana F. Souza, Joao C. P. Ferreira, Simone B. Chiacchio, Luiz H. A. Machado

Abstract:

Neonatal conjunctivitis, or ophthalmia, is an infection of the conjunctiva or cornea before opening the eyelids. It is believed that immunodeficiency contributes to the development of the condition. This study aims at reporting a case of ophthalmia neonatorum in a dog, in addition to its diagnosis and treatment. A litter of five pug neonates was admitted to the Sao Paulo State University (UNESP) Veterinary Hospital, Botucatu, Sao Paulo, Brazil, with complaints of ocular secretion. The neonates were five days old. The clinical examination revealed that three newborns presented swelling in the ocular region and a purulent secretion in the medial corner of the eye that was exerting pressure on the ocular globes, which are compatible with the description of this disease. The diagnosis was made based on the clinical signs and bacterial culture of the secretion, which revealed the presence of bacteria belonging to the genus Staphylococcus sp. The laboratory assays did not reveal any alterations. The treatment was instituted gently, opening the eyelids early and cleaning the purulent ocular secretion with saline solution. An ophthalmic ointment with retinol, amino acids, methionine, and chloramphenicol (Epitezan®) was prescribed four times a day for seven days. Blood plasma (2 mL/100 g) was administered subcutaneously because bacterial infections in neonates may represent a failure in the transference of passive immunity. A more thorough cleaning of the environment was also recommended. Neonatal conjunctivitis has a simple diagnosis and treatment. If not treated early, it can evolve to adherence of the eyelids to the cornea, ulceration, and perforation of the cornea. Therefore, the prognosis is favorable as long as the condition is diagnosed early, and the treatment is instituted quickly.

Keywords: ophthalmia neonatorum, neonatal infection, puppy, newborn

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2439 Reinforced Concrete Foundation for Turbine Generators

Authors: Siddhartha Bhattacharya

Abstract:

Steam Turbine-Generators (STG) and Combustion Turbine-Generator (CTG) are used in almost all modern petrochemical, LNG plants and power plant facilities. The reinforced concrete table top foundations are required to support these high speed rotating heavy machineries and is one of the most critical and challenging structures on any industrial project. The paper illustrates through a practical example, the step by step procedure adopted in designing a table top foundation supported on piles for a steam turbine generator with operating speed of 60 Hz. Finite element model of a table top foundation is generated in ANSYS. Piles are modeled as springs-damper elements (COMBIN14). Basic loads are adopted in analysis and design of the foundation based on the vendor requirements, industry standards, and relevant ASCE & ACI codal provisions. Static serviceability checks are performed with the help of Misalignment Tolerance Matrix (MTM) method in which the percentage of misalignment at a given bearing due to displacement at another bearing is calculated and kept within the stipulated criteria by the vendor so that the machine rotor can sustain the stresses developed due to this misalignment. Dynamic serviceability checks are performed through modal and forced vibration analysis where the foundation is checked for resonance and allowable amplitudes, as stipulated by the machine manufacturer. Reinforced concrete design of the foundation is performed by calculating the axial force, bending moment and shear at each of the critical sections. These values are calculated through area integral of the element stresses at these critical locations. Design is done as per ACI 318-05.

Keywords: steam turbine generator foundation, finite element, static analysis, dynamic analysis

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2438 Idiopathic Gingival Fibromatosis

Authors: Bandana Koirala, Shivalal Sharma

Abstract:

Introduction: Gingival enlargements are quite common and may be either inflammatory, non-inflammatory or a combination of both. Idiopathic gingival enlargement is a rare condition with a proliferative fibrous lesion of the gingival tissue that causes esthetic and functional problems. It is of undetermined etiology. Case Description: This case report addresses the diagnosis and treatment of a case of idiopathic gingival enlargement in a 9-year-old male patient. The patient presented with a generalized diffuse gingival enlargement involving the entire maxillary and the mandibular arch with extension on occlusal, buccal, lingual, and palatal surfaces with just parts of occlusal surfaces of few upper and lower molars visible resulting in open mouth, difficulty in mastication and speech. Biopsy report confirmed the diagnosis of fibromatosis gingivae. Gingivectomy was carried out in all four quadrants by using external bevel incision. Conclusion: Though total esthetics could not be restored due to unusual bony enlargement, the general appearance improved satisfactorily. Treatment after complete excision however, improved the masticatory competence to a great extent.

Keywords: idiopathic gingival fibromatosis, gingival enlargement, gingivectomy, medical and health sciences

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2437 Evaluating the Diagnostic Accuracy of the ctDNA Methylation for Liver Cancer

Authors: Maomao Cao

Abstract:

Objective: To test the performance of ctDNA methylation for the detection of liver cancer. Methods: A total of 1233 individuals have been recruited in 2017. 15 male and 15 female samples (including 10 cases of liver cancer) were randomly selected in the present study. CfDNA was extracted by MagPure Circulating DNA Maxi Kit. The concentration of cfDNA was obtained by Qubit™ dsDNA HS Assay Kit. A pre-constructed predictive model was used to analyze methylation data and to give a predictive score for each cfDNA sample. Individuals with a predictive score greater than or equal to 80 were classified as having liver cancer. CT tests were considered the gold standard. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for the diagnosis of liver cancer were calculated. Results: 9 patients were diagnosed with liver cancer according to the prediction model (with high sensitivity and threshold of 80 points), with scores of 99.2, 91.9, 96.6, 92.4, 91.3, 92.5, 96.8, 91.1, and 92.2, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of ctDNA methylation for the diagnosis of liver cancer were 0.70, 0.90, 0.78, and 0.86, respectively. Conclusions: ctDNA methylation could be an acceptable diagnostic modality for the detection of liver cancer.

Keywords: liver cancer, ctDNA methylation, detection, diagnostic performance

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2436 A Hybrid Fuzzy Clustering Approach for Fertile and Unfertile Analysis

Authors: Shima Soltanzadeh, Mohammad Hosain Fazel Zarandi, Mojtaba Barzegar Astanjin

Abstract:

Diagnosis of male infertility by the laboratory tests is expensive and, sometimes it is intolerable for patients. Filling out the questionnaire and then using classification method can be the first step in decision-making process, so only in the cases with a high probability of infertility we can use the laboratory tests. In this paper, we evaluated the performance of four classification methods including naive Bayesian, neural network, logistic regression and fuzzy c-means clustering as a classification, in the diagnosis of male infertility due to environmental factors. Since the data are unbalanced, the ROC curves are most suitable method for the comparison. In this paper, we also have selected the more important features using a filtering method and examined the impact of this feature reduction on the performance of each methods; generally, most of the methods had better performance after applying the filter. We have showed that using fuzzy c-means clustering as a classification has a good performance according to the ROC curves and its performance is comparable to other classification methods like logistic regression.

Keywords: classification, fuzzy c-means, logistic regression, Naive Bayesian, neural network, ROC curve

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2435 A Systematic Review on Factors/Predictors and Outcomes of Parental Distress in Childhood Acute Lymphoblastic Leukemia

Authors: Ana Ferraz, Martim Santos, M. Graça Pereira

Abstract:

Distress among parents of children with acute lymphoblastic leukemia (ALL) is common during treatment and can persist several years post-diagnosis, impacting the adjustment of children and parents themselves. Current evidence is needed to examine the scope and nature of parental distress in childhood ALL. This review focused on associated variables, predictors, and outcomes of parental distress following their ALL diagnosis of their child. PubMed, Web of Science, and PsycINFO databases were searched for English and Spanish papers published from 1983 to 2021. PRISMA statement was followed, and papers were evaluated through a standardized methodological quality assessment tool (NHLBI). Of the 28 papers included, 16 were evaluated as fair, eight as good, and four as poor. Regarding results, 11 papers reported subgroup differences, and 15 found potential predictors of parental distress, including sociodemographic, psychosocial, psychological, family, health, and ALL-specific variables. Significant correlations were found between parental distress, social support, illness cognitions, and resilience, as well as contradictory results regarding the impact of sociodemographic variables on parental distress. Family cohesion and caregiver burden were associated with distress, and the use of healthy coping strategies was associated with less anxiety. Caregiver strain contributed to distress, and the overall impact of illness positively predicted anxiety in mothers and somatization in fathers. Differences in parental distress were found regarding group risk, time since diagnosis, and treatment phases. Thirteen papers explored the outcomes of parental distress on psychological, family, health, and social/education outcomes. Parental distress was the most important predictor of family strain. Significant correlations were found between parental distress at diagnosis and further psychological adjustment of parents themselves and their children. Most papers reported correlations between parental distress on children’s adjustment and quality of life, although few studies reported no association. Correlations between maternal depression and child participation in education and social life were also found. Longitudinal studies are needed to better understand parental distress and its consequences on health outcomes, in particular. Future interventions should focus mainly on parents on distress reduction and psychological adjustment, both in parents and children over time.

Keywords: childhood acute lymphoblastic leukemia, family, parental distress, psychological adjustment, quality of life

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2434 Rare Differential Diagnostic Dilemma

Authors: Angelis P. Barlampas

Abstract:

Theoretical background Disorders of fixation and rotation of the large intestine, result in the existence of its parts in ectopic anatomical positions. In case of symptomatology, the clinical picture is complicated by the possible symptomatology of the neighboring anatomical structures and a differential diagnostic problem arises. Target The purpose of this work is to demonstrate the difficulty of revealing the real cause of abdominal pain, in cases of anatomical variants and the decisive contribution of imaging and especially that of computed tomography. Methods A patient came to the emergency room, because of acute pain in the right hypochondrium. Clinical examination revealed tenderness in the gallbladder area and a positive Murphy's sign. An ultrasound exam depicted a normal gallbladder and the patient was referred for a CT scan. Results Flexible, unfixed ascending colon and cecum, located in the anatomical region of the right mesentery. Opacities of the surrounding peritoneal fat and a small linear concentration of fluid can be seen. There was an appendix of normal anteroposterior diameter with the presence of air in its lumen and without clear signs of inflammation. There was an impression of possible inflammatory swelling at the base of the appendix, (DD phenomenon of partial volume; e.t.c.). Linear opacities of the peritoneal fat in the region of the second loop of the duodenum. Multiple diverticula throughout the colon. Differential Diagnosis The differential diagnosis includes the following: Inflammation of the base of the appendix, diverticulitis of the cecum-ascending colon, a rare case of second duodenal loop ulcer, tuberculosis, terminal ileitis, pancreatitis, torsion of unfixed cecum-ascending colon, embolism or thrombosis of a vascular intestinal branch. Final Diagnosis There is an unfixed cecum-ascending colon, which is exhibiting diverticulitis.

Keywords: unfixed cecum-ascending colon, abdominal pain, malrotation, abdominal CT, congenital anomalies

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2433 Somatic Delusional Disorder Subsequent to Phantogeusia: A Case Report

Authors: Pedro Felgueiras, Ana Miguel, Nélson Almeida, Raquel Silva

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Objective: Through the study of a clinical case of delusional somatic disorder secondary to phantogeusia, we aim to highlight the importance of considering psychosomatic conditions in differential diagnosis, as well as to emphasize the complexity of its comprehension, treatment, and respective impact on patients’ functioning. Methods: Bearing this in mind, we conducted a critical analysis of a case series based on patient observations, clinical data, and complementary diagnostic methods, as well as a non-systematic review of the literature on the subject. Results: A 61-year-old female patient with no history of psychiatric conditions. Family psychiatric history of mood disorder (depression), with psychotic features found in her mother. Medical history of many comorbidities affecting different organ systems (endocrine, gastrointestinal, genitourinary, ophthalmological). Documented neuroticism traits of personality. The patient’s family described a persistent concern about several physical symptoms across her life, with a continuous effort to obtain explanations about any sensation out of her normal perception. Since being subjected to endoscopy in 2018, she started complaints of persistent phantogeusia (acid taste) and developed excessive thoughts, feelings, and behaviors associated with this somatic symptom. The patient was evaluated by several medical specialties, and an extensive panel of medical exams was carried out, excluding any disease. Besides all the investigation and with no evidence of disease signs, acute anxiety, time, and energy dispended to this symptom culminated in severe psychosocial impairment. The patient was admitted to a psychiatric ward for investigation and treatment of this clinical picture, leading to the diagnosis of the delusional somatic disorder. In order to exclude the acute organic etiology of this psychotic disorder, an analytic panel was carried out with no abnormal results. In the context of a psychotic clinical picture, a CT scan was performed, which revealed a right cortical vascular lesion. Neuropsychological evaluation was made, with the description of cognitive functioning being globally normative. During treatment with an antipsychotic (pimozide), a complete remission of the somatic delusion was associated with the disappearance of gustative perception disturbance. In follow-up, a relapse of gustative sensation was documented, and her thoughts and speech were dominated by concerns about multiple somatic symptoms. Conclusion: In terms of abnormal bodily sensations, the oral cavity is one of the frequent sites of delusional disorder. Patients with these gustatory perception distortions complain about unusual sensations without corresponding abnormal findings in the oral area. Its pathophysiology has not been fully elucidated yet. In terms of its comprehensive psychopathology, this case was hypothesized as a paranoid development of a delusional somatic disorder triggered by a post-invasive procedure phantogeusia (which is described as a possible side effect of an endoscopy) in a patient with an anankastic personality. This case presents interesting psychopathology, reinforcing the complexity of psychosomatic disorders in terms of their etiopathogenesis, clinical treatment, and long-term prognosis.

Keywords: psychosomatics, delusional somatic disorder, phantogeusia, paranoid development

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2432 Comparison of Computed Tomography Dose Index, Dose Length Product and Effective Dose Among Male and Female Patients From Contrast Enhanced Computed Tomography Pancreatitis Protocol

Authors: Babina Aryal

Abstract:

Background: The diagnosis of pancreatitis is generally based on clinical and laboratory findings; however, Computed Tomography (CT) is an imaging technique of choice specially Contrast Enhanced Computed Tomography (CECT) shows morphological characteristic findings that allow for establishing the diagnosis of pancreatitis and determining the extent of disease severity which is done along with the administration of appropriate contrast medium. The purpose of this study was to compare Computed Tomography Dose Index (CTDI), Dose Length Product (DLP) and Effective Dose (ED) among male and female patients from Contrast Enhanced Computed Tomography (CECT) Pancreatitis Protocol. Methods: This retrospective study involved data collection based on clinical/laboratory/ultrasonography diagnosis of Pancreatitis and has undergone CECT Abdomen pancreatitis protocol. data collection involved detailed information about a patient's Age and Gender, Clinical history, Individual Computed Tomography Dose Index and Dose Length Product and effective dose. Results: We have retrospectively collected dose data from 150 among which 127 were males and 23 were females. The values obtained from the display of the CT screen were measured, calculated and compared to determine whether the CTDI, DLP and ED values were similar or not. CTDI for females was more as compared to males. The differences in CTDI values for females and males were 32.2087 and 37.1609 respectively. DLP values and Effective dose for both the genders did not show significant differences. Conclusion: This study concluded that there were no more significant changes in the DLP and ED values among both the genders however we noticed that female patients had more CTDI than males.

Keywords: computed tomography, contrast enhanced computed tomography, computed tomography dose index, dose length product, effective dose

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2431 Clinical Characteristics of Children Presenting with History of Child Sexual Abuse to a Tertiary Care Centre in India

Authors: T. S. Sowmya Bhaskaran, Shekhar Seshadri

Abstract:

This study aims to study the clinical features of with a history of Child Sexual Abuse (CSA). A chart review of 40 children (<16 years) with history of CSA evaluated at the Department of Child and Adolescent Psychiatry of NIMHANS during a two year period was performed. Results:The most common form of abuse was contact penetrative abuse (65%) followed by non-contact penetrative abuse (32.5%). 75% (N=30) had a psychiatric diagnosis at baseline. 50% of these children had one or more psychiatric comorbidities. Anxiety disorder was the most common diagnosis (27.5%) which included PTSD (11%) followed by Depressive disorder (25.2%). Children abused by multiple perpetrators were found to be more likely to have depression, to having a comorbid psychiatric disorder and more prone to exhibit sexualized behaviour. Children who also experienced physical violence at home were more likely to develop psychiatric illness following child sexual abuse. Psychiatric morbidity is high in clinic population of children with history of CSA. It is important to increase the awareness regarding the consequences of CSA in order to increase help seeking.

Keywords: child sexual abuse, India, tertiary care centre, clinical characteristics

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2430 Generative Adversarial Network for Bidirectional Mappings between Retinal Fundus Images and Vessel Segmented Images

Authors: Haoqi Gao, Koichi Ogawara

Abstract:

Retinal vascular segmentation of color fundus is the basis of ophthalmic computer-aided diagnosis and large-scale disease screening systems. Early screening of fundus diseases has great value for clinical medical diagnosis. The traditional methods depend on the experience of the doctor, which is time-consuming, labor-intensive, and inefficient. Furthermore, medical images are scarce and fraught with legal concerns regarding patient privacy. In this paper, we propose a new Generative Adversarial Network based on CycleGAN for retinal fundus images. This method can generate not only synthetic fundus images but also generate corresponding segmentation masks, which has certain application value and challenge in computer vision and computer graphics. In the results, we evaluate our proposed method from both quantitative and qualitative. For generated segmented images, our method achieves dice coefficient of 0.81 and PR of 0.89 on DRIVE dataset. For generated synthetic fundus images, we use ”Toy Experiment” to verify the state-of-the-art performance of our method.

Keywords: retinal vascular segmentations, generative ad-versarial network, cyclegan, fundus images

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2429 Behavioral Study Circumferential and Longitudinal Cracks in a Steel Pipeline X65 and Repair Patch

Authors: Sadok Aboubakr

Abstract:

The mechanical behavior of cracks from several manufacturing defect in an oil pipeline, is characterized by the fact that defects'm taking several forms: circumferential, longitudinal and inclined crack that evolve over time. Increased lifetime of the constructions and in particular cylindrical tubes under internal pressure requires knowledge improving these defects during loading. From this study we simulated various forms of cracking and also their pipeline repair patch.

Keywords: stress intensity factor, pressure, Young's modulus, Poisson's ratio, Shear modulus, Longueur du pipeline, the angle of crack, crack length

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2428 Geophysical Methods of Mapping Groundwater Aquifer System: Perspectives and Inferences From Lisana Area, Western Margin of the Central Main Ethiopian Rift

Authors: Esubalew Yehualaw Melaku, Tigistu Haile Eritro

Abstract:

In this study, two basic geophysical methods are applied for mapping the groundwater aquifer system in the Lisana area along the Guder River, northeast of Hosanna town, near the western margin of the Central Main Ethiopian Rift. The main target of the study is to map the potential aquifer zone and investigate the groundwater potential for current and future development of the resource in the Gode area. The geophysical methods employed in this study include, Vertical Electrical Sounding (VES) and magnetic survey techniques. Electrical sounding was used to examine and map the depth to the potential aquifer zone of the groundwater and its distribution over the area. On the other hand, a magnetic survey was used to delineate contact between lithologic units and geological structures. The 2D magnetic modeling and the geoelectric sections are used for the identification of weak zones, which control the groundwater flow and storage system. The geophysical survey comprises of twelve VES readings collected by using a Schlumberger array along six profile lines and more than four hundred (400) magnetic readings at about 10m station intervals along four profiles and 20m along three random profiles. The study result revealed that the potential aquifer in the area is obtained at a depth range from 45m to 92m. This is the response of the highly weathered/ fractured ignimbrite and pumice layer with sandy soil, which is the main water-bearing horizon. Overall, in the neighborhood of four VES points, VES- 2, VES- 3, VES-10, and VES-11, shows good water-bearing zones in the study area.

Keywords: vertical electrical sounding, magnetic survey, aquifer, groundwater potential

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2427 Application of Artificial Neural Network Technique for Diagnosing Asthma

Authors: Azadeh Bashiri

Abstract:

Introduction: Lack of proper diagnosis and inadequate treatment of asthma leads to physical and financial complications. This study aimed to use data mining techniques and creating a neural network intelligent system for diagnosis of asthma. Methods: The study population is the patients who had visited one of the Lung Clinics in Tehran. Data were analyzed using the SPSS statistical tool and the chi-square Pearson's coefficient was the basis of decision making for data ranking. The considered neural network is trained using back propagation learning technique. Results: According to the analysis performed by means of SPSS to select the top factors, 13 effective factors were selected, in different performances, data was mixed in various forms, so the different models were made for training the data and testing networks and in all different modes, the network was able to predict correctly 100% of all cases. Conclusion: Using data mining methods before the design structure of system, aimed to reduce the data dimension and the optimum choice of the data, will lead to a more accurate system. Therefore, considering the data mining approaches due to the nature of medical data is necessary.

Keywords: asthma, data mining, Artificial Neural Network, intelligent system

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2426 Investigation into the Effectiveness of Bacillus Mucilaginosus in Liberation of Platinum Group Metals Locked in Silicates

Authors: Nokubonga G. Zulu, Bongephiwe M. Thethwayo, Mapilane S. Madiba, Peter A. Olubambi

Abstract:

In South Africa, PGMs’ metallurgy industry is now leaned on the Upper Group 2 (UG2) reef for the beneficiation of 4PGEs (Platinum, Palladium, Rhodium, and Ruthenium). The current effective beneficiation method is direct froth flotation which uses the hydrophobicity of liberated valuables minerals to carefully float them while hydrophilic gangue minerals report to the residue. PGMs are known to be associated with base metal sulphides which are hydrophobic; however, approximately 25% of PGMs from UG2 are associated with hydrophilic silicates, which results in high PGMs grade in the flotation residue. Further, the smallest size in which UG2 PGMs occur is approximately 9 microns which demands high grinding for liberation, imposing energy and cost implications. The use of Bacillus mucilaginosus to liberate PGMs using Bio-leaching of PGMs bearing Silicates is a promising cost-effective, energy-saving, and green solution to liberate PGMs locked in silicates. This is due to the ability of Bacillus mucilaginosus to generate extracellular polysaccharides (EPS) that are responsible for the leaching of silicate minerals. The bioleaching is done at a laboratory beaker using a cultivated Bacillus mucilaginosus as a lixiviant. The bioleaching residue is expected to have a reduced particle size due to silicate consumption, which reduces the need and cost associated with a secondary milling circuit. Moreover, the grade of the bioleaching product is increased since the silicates (gangue minerals) are consumed by Bacillus mucilaginosus; this serves as a pre-concentration step. This paper discusses an alternative liberation and pre-concentrating technique of PGMs that are associated with silicates using Bacillus mucilaginosus leaching to dissolve silicates.

Keywords: Bacillus mucilaginosus, bio-leaching of PGMs bearing silicates, liberation of PGMs, pre-concentration of PGMs

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2425 Prediction of California Bearing Ratio of a Black Cotton Soil Stabilized with Waste Glass and Eggshell Powder using Artificial Neural Network

Authors: Biruhi Tesfaye, Avinash M. Potdar

Abstract:

The laboratory test process to determine the California bearing ratio (CBR) of black cotton soils is not only overpriced but also time-consuming as well. Hence advanced prediction of CBR plays a significant role as it is applicable In pavement design. The prediction of CBR of treated soil was executed by Artificial Neural Networks (ANNs) which is a Computational tool based on the properties of the biological neural system. To observe CBR values, combined eggshell and waste glass was added to soil as 4, 8, 12, and 16 % of the weights of the soil samples. Accordingly, the laboratory related tests were conducted to get the required best model. The maximum CBR value found at 5.8 at 8 % of eggshell waste glass powder addition. The model was developed using CBR as an output layer variable. CBR was considered as a function of the joint effect of liquid limit, plastic limit, and plastic index, optimum moisture content and maximum dry density. The best model that has been found was ANN with 5, 6 and 1 neurons in the input, hidden and output layer correspondingly. The performance of selected ANN has been 0.99996, 4.44E-05, 0.00353 and 0.0067 which are correlation coefficient (R), mean square error (MSE), mean absolute error (MAE) and root mean square error (RMSE) respectively. The research presented or summarized above throws light on future scope on stabilization with waste glass combined with different percentages of eggshell that leads to the economical design of CBR acceptable to pavement sub-base or base, as desired.

Keywords: CBR, artificial neural network, liquid limit, plastic limit, maximum dry density, OMC

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2424 Static Eccentricity Fault Diagnosis in Synchronous Reluctance Motor and Permanent Magnet Assisted Synchronous Reluctance Motor

Authors: M. Naeimi, H. Aghazadeh, E. Afjei, A. Siadatan

Abstract:

In this paper, a novel view of air gap magnetic field analysis of synchronous reluctance motor and permanent magnet assisted synchronous reluctance motor under static eccentricity to provide the precise fault diagnosis based on three-dimensional finite element method is presented. Analytical nature of this method makes it possible to simulate reliable and precise model by considering the end effects and axial fringing effects. The results of the three-dimensional finite element analysis of synchronous reluctance motor and permanent magnet synchronous reluctance motor such as flux linkage, flux density, and compression both of SynRM and PM-SynRM for various eccentric motor conditions are obtained and analyzed. These results present useful information regarding to the detection of static eccentricity.

Keywords: synchronous reluctance motor (SynRM), permanent magnet assisted synchronous reluctance motor (PMaSynRM), finite element method, static eccentricity, fault analysis

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2423 Photobleaching Kinetics and Epithelial Distribution of Hexylaminoleuilinate Induced PpIX in Rat Bladder Cancer

Authors: Sami El Khatib, Agnès Leroux, Jean-Louis Merlin, François Guillemin, Marie-Ange D’Hallewin

Abstract:

Photodynamic therapy (PDT) is a treatment modality based on the cytotoxic effect occurring on the target tissues by interaction of a photosensitizer with light in the presence of oxygen. One of the major advances in PDT can be attributed to the use of topical aminolevulinic (ALA) to induce Protoporphyrin IX (PpIX) for the treatment of early stage cancers as well as diagnosis. ALA is a precursor of the heme synthesis pathway. Locally delivered to the target tissue ALA overcomes the negative feedback exerted by heme and promotes the transient formation of PpIX in situ to reach critical effective levels in cells and tissue. Whereas early steps of the heme pathway occur in the cytosol, PpIX synthesis is shown to be held in the mitochondrial membranes and PpIX fluorescence is expected to accumulate in close vicinity of the initial building site and to progressively diffuse to the neighboring cytoplasmic compartment or other lipophylic organelles. PpIX is known to be highly reactive and will be degraded when irradiated with light. PpIX photobleaching is believed to be governed by a singlet oxygen mediated mechanism in the presence of oxidized amino acids and proteins. PpIX photobleaching and subsequent spectral phototransformation were described widely in tumor cells incubated in vitro with ALA solution, or ex vivo in human and porcine mucosa superfused with hexylaminolevulinate (hALA). PpIX photobleaching was also studied in vivo, using animal models such as normal or tumor mice skin and orthotopic rat bladder model. Hexyl aminolevulinate a more potent lipophilic derivative of ALA was proposed as an adjunct to standard cystoscopy in the fluorescence diagnosis of bladder cancer and other malignancies. We have previously reported the effectiveness of hALA mediated PDT of rat bladder cancer. Although normal and tumor bladder epithelium exhibit similar fluorescence intensities after intravesical instillation of two hALA concentrations (8 and 16 mM), the therapeutic response at 8mM and 20J/cm2 was completely different from the one observed at 16mM irradiated with the same light dose. Where the tumor is destroyed, leaving the underlying submucosa and muscle intact after an 8 mM instillation, 16mM sensitization and subsequent illumination results in the complete destruction of the underlying bladder wall but leaves the tumor undamaged. The object of the current study is to try to unravel the underlying mechanism for this apparent contradiction. PpIX extraction showed identical amounts of photosensitizer in tumor bearing bladders at both concentrations. Photobleaching experiments revealed mono-exponential decay curves in both situations but with a two times faster decay constant in case of 16mM bladders. Fluorescence microscopy shows an identical fluorescence pattern for normal bladders at both concentrations and tumor bladders at 8mM with bright spots. Tumor bladders at 16 mM exhibit a more diffuse cytoplasmic fluorescence distribution. The different response to PDT with regard to the initial pro-drug concentration can thus be attributed to the different cellular localization.

Keywords: bladder cancer, hexyl-aminolevulinate, photobleaching, confocal fluorescence microscopy

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2422 A Multi-Output Network with U-Net Enhanced Class Activation Map and Robust Classification Performance for Medical Imaging Analysis

Authors: Jaiden Xuan Schraut, Leon Liu, Yiqiao Yin

Abstract:

Computer vision in medical diagnosis has achieved a high level of success in diagnosing diseases with high accuracy. However, conventional classifiers that produce an image to-label result provides insufficient information for medical professionals to judge and raise concerns over the trust and reliability of a model with results that cannot be explained. In order to gain local insight into cancerous regions, separate tasks such as imaging segmentation need to be implemented to aid the doctors in treating patients, which doubles the training time and costs which renders the diagnosis system inefficient and difficult to be accepted by the public. To tackle this issue and drive AI-first medical solutions further, this paper proposes a multi-output network that follows a U-Net architecture for image segmentation output and features an additional convolutional neural networks (CNN) module for auxiliary classification output. Class activation maps are a method of providing insight into a convolutional neural network’s feature maps that leads to its classification but in the case of lung diseases, the region of interest is enhanced by U-net-assisted Class Activation Map (CAM) visualization. Therefore, our proposed model combines image segmentation models and classifiers to crop out only the lung region of a chest X-ray’s class activation map to provide a visualization that improves the explainability and is able to generate classification results simultaneously which builds trust for AI-led diagnosis systems. The proposed U-Net model achieves 97.61% accuracy and a dice coefficient of 0.97 on testing data from the COVID-QU-Ex Dataset which includes both diseased and healthy lungs.

Keywords: multi-output network model, U-net, class activation map, image classification, medical imaging analysis

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2421 Magnetic Single-Walled Carbon Nanotubes (SWCNTs) as Novel Theranostic Nanocarriers: Enhanced Targeting and Noninvasive MRI Tracking

Authors: Achraf Al Faraj, Asma Sultana Shaik, Baraa Al Sayed

Abstract:

Specific and effective targeting of drug delivery systems (DDS) to cancerous sites remains a major challenge for a better diagnostic and therapy. Recently, SWCNTs with their unique physicochemical properties and the ability to cross the cell membrane show promising in the biomedical field. The purpose of this study was first to develop a biocompatible iron oxide tagged SWCNTs as diagnostic nanoprobes to allow their noninvasive detection using MRI and their preferential targeting in a breast cancer murine model by placing an optimized flexible magnet over the tumor site. Magnetic targeting was associated to specific antibody-conjugated SWCNTs active targeting. The therapeutic efficacy of doxorubicin-conjugated SWCNTs was assessed, and the superiority of diffusion-weighted (DW-) MRI as sensitive imaging biomarker was investigated. Short Polyvinylpyrrolidone (PVP) stabilized water soluble SWCNTs were first developed, tagged with iron oxide nanoparticles and conjugated with Endoglin/CD105 monoclonal antibodies. They were then conjugated with doxorubicin drugs. SWCNTs conjugates were extensively characterized using TEM, UV-Vis spectrophotometer, dynamic light scattering (DLS) zeta potential analysis and electron spin resonance (ESR) spectroscopy. Their MR relaxivities (i.e. r1 and r2*) were measured at 4.7T and their iron content and metal impurities quantified using ICP-MS. SWCNTs biocompatibility and drug efficacy were then evaluated both in vitro and in vivo using a set of immunological assays. Luciferase enhanced bioluminescence 4T1 mouse mammary tumor cells (4T1-Luc2) were injected into the right inguinal mammary fat pad of Balb/c mice. Tumor bearing mice received either free doxorubicin (DOX) drug or SWCNTs with or without either DOX or iron oxide nanoparticles. A multi-pole 10x10mm high-energy flexible magnet was maintained over the tumor site during 2 hours post-injections and their properties and polarity were optimized to allow enhanced magnetic targeting of SWCNTs toward the primary tumor site. Tumor volume was quantified during the follow-up investigation study using a fast spin echo MRI sequence. In order to detect the homing of SWCNTs to the main tumor site, susceptibility-weighted multi-gradient echo (MGE) sequence was used to generate T2* maps. Apparent diffusion coefficient (ADC) measurements were also performed as a sensitive imaging biomarker providing early and better assessment of disease treatment. At several times post-SWCNT injection, histological analysis were performed on tumor extracts and iron-loaded SWCNT were quantified using ICP-MS in tumor sites, liver, spleen, kidneys, and lung. The optimized multi-poles magnet revealed an enhanced targeting of magnetic SWCNTs to the primary tumor site, which was found to be much higher than the active targeting achieved using antibody-conjugated SWCNTs. Iron-loading allowed their sensitive noninvasive tracking after intravenous administration using MRI. The active targeting of doxorubicin through magnetic antibody-conjugated SWCNTs nanoprobes was found to considerably decrease the primary tumor site and may have inhibited the development of metastasis in the tumor-bearing mice lung. ADC measurements in DW-MRI were found to significantly increase in a time-dependent manner after the injection of DOX-conjugated SWCNTs complexes.

Keywords: single-walled carbon nanotubes, nanomedicine, magnetic resonance imaging, cancer diagnosis and therapy

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2420 Identifying Degradation Patterns of LI-Ion Batteries from Impedance Spectroscopy Using Machine Learning

Authors: Yunwei Zhang, Qiaochu Tang, Yao Zhang, Jiabin Wang, Ulrich Stimming, Alpha Lee

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Forecasting the state of health and remaining useful life of Li-ion batteries is an unsolved challenge that limits technologies such as consumer electronics and electric vehicles. Here we build an accurate battery forecasting system by combining electrochemical impedance spectroscopy (EIS) -- a real-time, non-invasive and information-rich measurement that is hitherto underused in battery diagnosis -- with Gaussian process machine learning. We collect over 20,000 EIS spectra of commercial Li-ion batteries at different states of health, states of charge and temperatures -- the largest dataset to our knowledge of its kind. Our Gaussian process model takes the entire spectrum as input, without further feature engineering, and automatically determines which spectral features predict degradation. Our model accurately predicts the remaining useful life, even without complete knowledge of past operating conditions of the battery. Our results demonstrate the value of EIS signals in battery management systems.

Keywords: battery degradation, machine learning method, electrochemical impedance spectroscopy, battery diagnosis

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2419 Evaluation of Classification Algorithms for Diagnosis of Asthma in Iranian Patients

Authors: Taha SamadSoltani, Peyman Rezaei Hachesu, Marjan GhaziSaeedi, Maryam Zolnoori

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Introduction: Data mining defined as a process to find patterns and relationships along data in the database to build predictive models. Application of data mining extended in vast sectors such as the healthcare services. Medical data mining aims to solve real-world problems in the diagnosis and treatment of diseases. This method applies various techniques and algorithms which have different accuracy and precision. The purpose of this study was to apply knowledge discovery and data mining techniques for the diagnosis of asthma based on patient symptoms and history. Method: Data mining includes several steps and decisions should be made by the user which starts by creation of an understanding of the scope and application of previous knowledge in this area and identifying KD process from the point of view of the stakeholders and finished by acting on discovered knowledge using knowledge conducting, integrating knowledge with other systems and knowledge documenting and reporting.in this study a stepwise methodology followed to achieve a logical outcome. Results: Sensitivity, Specifity and Accuracy of KNN, SVM, Naïve bayes, NN, Classification tree and CN2 algorithms and related similar studies was evaluated and ROC curves were plotted to show the performance of the system. Conclusion: The results show that we can accurately diagnose asthma, approximately ninety percent, based on the demographical and clinical data. The study also showed that the methods based on pattern discovery and data mining have a higher sensitivity compared to expert and knowledge-based systems. On the other hand, medical guidelines and evidence-based medicine should be base of diagnostics methods, therefore recommended to machine learning algorithms used in combination with knowledge-based algorithms.

Keywords: asthma, datamining, classification, machine learning

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2418 Hybridization of Manually Extracted and Convolutional Features for Classification of Chest X-Ray of COVID-19

Authors: M. Bilal Ishfaq, Adnan N. Qureshi

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COVID-19 is the most infectious disease these days, it was first reported in Wuhan, the capital city of Hubei in China then it spread rapidly throughout the whole world. Later on 11 March 2020, the World Health Organisation (WHO) declared it a pandemic. Since COVID-19 is highly contagious, it has affected approximately 219M people worldwide and caused 4.55M deaths. It has brought the importance of accurate diagnosis of respiratory diseases such as pneumonia and COVID-19 to the forefront. In this paper, we propose a hybrid approach for the automated detection of COVID-19 using medical imaging. We have presented the hybridization of manually extracted and convolutional features. Our approach combines Haralick texture features and convolutional features extracted from chest X-rays and CT scans. We also employ a minimum redundancy maximum relevance (MRMR) feature selection algorithm to reduce computational complexity and enhance classification performance. The proposed model is evaluated on four publicly available datasets, including Chest X-ray Pneumonia, COVID-19 Pneumonia, COVID-19 CTMaster, and VinBig data. The results demonstrate high accuracy and effectiveness, with 0.9925 on the Chest X-ray pneumonia dataset, 0.9895 on the COVID-19, Pneumonia and Normal Chest X-ray dataset, 0.9806 on the Covid CTMaster dataset, and 0.9398 on the VinBig dataset. We further evaluate the effectiveness of the proposed model using ROC curves, where the AUC for the best-performing model reaches 0.96. Our proposed model provides a promising tool for the early detection and accurate diagnosis of COVID-19, which can assist healthcare professionals in making informed treatment decisions and improving patient outcomes. The results of the proposed model are quite plausible and the system can be deployed in a clinical or research setting to assist in the diagnosis of COVID-19.

Keywords: COVID-19, feature engineering, artificial neural networks, radiology images

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2417 A Next-Generation Pin-On-Plate Tribometer for Use in Arthroplasty Material Performance Research

Authors: Lewis J. Woollin, Robert I. Davidson, Paul Watson, Philip J. Hyde

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Introduction: In-vitro testing of arthroplasty materials is of paramount importance when ensuring that they can withstand the performance requirements encountered in-vivo. One common machine used for in-vitro testing is a pin-on-plate tribometer, an early stage screening device that generates data on the wear characteristics of arthroplasty bearing materials. These devices test vertically loaded rotating cylindrical pins acting against reciprocating plates, representing the bearing surfaces. In this study, a pin-on-plate machine has been developed that provides several improvements over current technology, thereby progressing arthroplasty bearing research. Historically, pin-on-plate tribometers have been used to investigate the performance of arthroplasty bearing materials under conditions commonly encountered during a standard gait cycle; nominal operating pressures of 2-6 MPa and an operating frequency of 1 Hz are typical. There has been increased interest in using pin-on-plate machines to test more representative in-vivo conditions, due to the drive to test 'beyond compliance', as well as their testing speed and economic advantages over hip simulators. Current pin-on-plate machines do not accommodate the increased performance requirements associated with more extreme kinematic conditions, therefore a next-generation pin-on-plate tribometer has been developed to bridge the gap between current technology and future research requirements. Methodology: The design was driven by several physiologically relevant requirements. Firstly, an increased loading capacity was essential to replicate the peak pressures that occur in the natural hip joint during running and chair-rising, as well as increasing the understanding of wear rates in obese patients. Secondly, the introduction of mid-cycle load variation was of paramount importance, as this allows for an approximation of the loads present in a gait cycle to be applied and to test the fatigue properties of materials. Finally, the rig must be validated against previous-generation pin-on-plate and arthroplasty wear data. Results: The resulting machine is a twelve station device that is split into three sets of four stations, providing an increased testing capacity compared to most current pin-on-plate tribometers. The loading of the pins is generated using a pneumatic system, which can produce contact pressures of up to 201 MPa on a 3.2 mm² round pin face. This greatly exceeds currently achievable contact pressures in literature and opens new research avenues such as testing rim wear of mal-positioned hip implants. Additionally, the contact pressure of each set can be changed independently of the others, allowing multiple loading conditions to be tested simultaneously. Using pneumatics also allows the applied pressure to be switched ON/OFF mid-cycle, another feature not currently reported elsewhere, which allows for investigation into intermittent loading and material fatigue. The device is currently undergoing a series of validation tests using Ultra-High-Molecular-Weight-Polyethylene pins and 316L Stainless Steel Plates (polished to a Ra < 0.05 µm). The operating pressures will be between 2-6 MPa, operating at 1 Hz, allowing for validation of the machine against results reported previously in the literature. The successful production of this next-generation pin-on-plate tribometer will, following its validation, unlock multiple previously unavailable research avenues.

Keywords: arthroplasty, mechanical design, pin-on-plate, total joint replacement, wear testing

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2416 Experimental and FEA Study for Reduction of Damage in Sheet Metal Forming

Authors: Amitkumar R. Shelar, B. P. Ronge, Sridevi Seshabhattar, R. M. Wabale

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This paper gives knowledge about the behavior of cold rolled steel IS 513_2008 CR2_D having grade D for the reduction of ductile damage. CR specifies Cold Rolled and D for Drawing grade. Problems encountered during sheet metal forming operations are dent, wrinkles, thinning, spring back, insufficient stretching etc. In this paper, wrinkle defect was studied experimentally and by using FE software on one of the auto components due to which its functionality was decreased. Experimental result and simulation result were found to be in agreement.

Keywords: deep drawing, FE software-LS DYNA, friction, wrinkling

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2415 Hypotonia - A Concerning Issue in Neonatal Care

Authors: Eda Jazexhiu-Postoli, Gladiola Hoxha, Ada Simeoni, Sonila Biba

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Background Neonatal hypotonia represents a commonly encountered issue in the Neonatal Intensive Care Unit and newborn nursery. The differential diagnosis is broad, encompassing chromosome abnormalities, primary muscular dystrophies, neuropathies and inborn errors of metabolism. Aim of study Our study describes some of the main clinical features of hypotonia in newborns and presents clinical cases of neonatal hypotonia we treated in our Neonatal unit in the last 3 years. Case reports Four neonates born in our hospital presented with hypotonia after birth, one preterm newborn 35-36 weeks of gestational age and three other term newborns (38-39 weeks of gestational age). Prenatal data revealed a decrease in fetal movements in both cases. Intrapartum meconium-stained amniotic fluid was found in 75% of our hypotonic newborns. Clinical features included inability to establish effective respiratory movements and need for resuscitation in the delivery room, respiratory distress syndrome, feeding difficulties and need for oro-gastric tube feeding, dysmorphic features, hoarse voice and moderate to severe muscular hypotonia. The genetic workup revealed the diagnosis of Autosomal Recessive Congenital Myasthenic Syndrome 1-B, Sotos Syndrome, Spinal Muscular Atrophy Type 1 and Transient Hypotonia of the Newborn. Two out of four hypotonic neonates were transferred to the Pediatric Intensive Care Unit and died at the age of three to five months old. Conclusion Hypotonia is a concerning finding in neonatal care and it is suggested by decreased intrauterine fetal movements, failure to establish first breaths, respiratory distress and feeding difficulties in the neonate. Prognosis is determined by its etiology and time of diagnosis and intervention.

Keywords: hypotonic neonate, respiratory distress, feeding difficulties, fetal movements

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2414 Communication of Expected Survival Time to Cancer Patients: How It Is Done and How It Should Be Done

Authors: Geir Kirkebøen

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Most patients with serious diagnoses want to know their prognosis, in particular their expected survival time. As part of the informed consent process, physicians are legally obligated to communicate such information to patients. However, there is no established (evidence based) ‘best practice’ for how to do this. The two questions explored in this study are: How do physicians communicate expected survival time to patients, and how should it be done? We explored the first, descriptive question in a study with Norwegian oncologists as participants. The study had a scenario and a survey part. In the scenario part, the doctors should imagine that a patient, recently diagnosed with a serious cancer diagnosis, has asked them: ‘How long can I expect to live with such a diagnosis? I want an honest answer from you!’ The doctors should assume that the diagnosis is certain, and that from an extensive recent study they had optimal statistical knowledge, described in detail as a right-skewed survival curve, about how long such patients with this kind of diagnosis could be expected to live. The main finding was that very few of the oncologists would explain to the patient the variation in survival time as described by the survival curve. The majority would not give the patient an answer at all. Of those who gave an answer, the typical answer was that survival time varies a lot, that it is hard to say in a specific case, that we will come back to it later etc. The survey part of the study clearly indicates that the main reason why the oncologists would not deliver the mortality prognosis was discomfort with its uncertainty. The scenario part of the study confirmed this finding. The majority of the oncologists explicitly used the uncertainty, the variation in survival time, as a reason to not give the patient an answer. Many studies show that patients want realistic information about their mortality prognosis, and that they should be given hope. The question then is how to communicate the uncertainty of the prognosis in a realistic and optimistic – hopeful – way. Based on psychological research, our hypothesis is that the best way to do this is by explicitly describing the variation in survival time, the (usually) right skewed survival curve of the prognosis, and emphasize to the patient the (small) possibility of being a ‘lucky outlier’. We tested this hypothesis in two scenario studies with lay people as participants. The data clearly show that people prefer to receive expected survival time as a median value together with explicit information about the survival curve’s right skewedness (e.g., concrete examples of ‘positive outliers’), and that communicating expected survival time this way not only provides people with hope, but also gives them a more realistic understanding compared with the typical way expected survival time is communicated. Our data indicate that it is not the existence of the uncertainty regarding the mortality prognosis that is the problem for patients, but how this uncertainty is, or is not, communicated and explained.

Keywords: cancer patients, decision psychology, doctor-patient communication, mortality prognosis

Procedia PDF Downloads 307
2413 Automatic Thresholding for Data Gap Detection for a Set of Sensors in Instrumented Buildings

Authors: Houda Najeh, Stéphane Ploix, Mahendra Pratap Singh, Karim Chabir, Mohamed Naceur Abdelkrim

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Building systems are highly vulnerable to different kinds of faults and failures. In fact, various faults, failures and human behaviors could affect the building performance. This paper tackles the detection of unreliable sensors in buildings. Different literature surveys on diagnosis techniques for sensor grids in buildings have been published but all of them treat only bias and outliers. Occurences of data gaps have also not been given an adequate span of attention in the academia. The proposed methodology comprises the automatic thresholding for data gap detection for a set of heterogeneous sensors in instrumented buildings. Sensor measurements are considered to be regular time series. However, in reality, sensor values are not uniformly sampled. So, the issue to solve is from which delay each sensor become faulty? The use of time series is required for detection of abnormalities on the delays. The efficiency of the method is evaluated on measurements obtained from a real power plant: an office at Grenoble Institute of technology equipped by 30 sensors.

Keywords: building system, time series, diagnosis, outliers, delay, data gap

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2412 Breast Cancer: The Potential of miRNA for Diagnosis and Treatment

Authors: Abbas Pourreza

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MicroRNAs (miRNAs) are small single-stranded non-coding RNAs. They are almost 18-25 nucleotides long and very conservative through evolution. They are involved in adjusting the expression of numerous genes due to the existence of a complementary region, generally in the 3' untranslated regions (UTR) of target genes, against particular mRNAs in the cell. Also, miRNAs have been proven to be involved in cell development, differentiation, proliferation, and apoptosis. More than 2000 miRNAs have been recognized in human cells, and these miRNAs adjust approximately one-third of all genes in human cells. Dysregulation of miRNA originated from abnormal DNA methylation patterns of the locus, cause to down-regulated or overexpression of miRNAs, and it may affect tumor formation or development of it. Breast cancer (BC) is the most commonly identified cancer, the most prevalent cancer (23%), and the second-leading (14%) mortality in all types of cancer in females. BC can be classified based on the status (+/−) of the hormone receptors, including estrogen receptor (ER), progesterone receptor (PR), and the Receptor tyrosine-protein kinase erbB-2 (ERBB2 or HER2). Currently, there are four main molecular subtypes of BC: luminal A, approximately 50–60 % of BCs; luminal B, 10–20 %; HER2 positive, 15–20 %, and 10–20 % considered Basal (triple-negative breast cancer (TNBC)) subtype. Aberrant expression of miR-145, miR-21, miR-10b, miR-125a, and miR-206 was detected by Stem-loop real-time RT-PCR in BC cases. Breast tumor formation and development may result from down-regulation of a tumor suppressor miRNA such as miR-145, miR-125a, and miR-206 and/or overexpression of an oncogenic miRNA such as miR-21 and miR-10b. MiR-125a, miR-206, miR-145, miR-21, and miR-10b are hugely predicted to be new tumor markers for the diagnosis and prognosis of BC. MiR-21 and miR-125a could play a part in the treatment of HER-2-positive breast cancer cells, while miR-145 and miR-206 could speed up the evolution of cure techniques for TNBC. To conclude, miRNAs will be presented as hopeful molecules to be used in the primary diagnosis, prognosis, and treatment of BC and battle as opposed to its developed drug resistance.

Keywords: breast cancer, HER2 positive, miRNA, TNBC

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2411 Functional Analysis of Variants Implicated in Hearing Loss in a Cohort from Argentina: From Molecular Diagnosis to Pre-Clinical Research

Authors: Paula I. Buonfiglio, Carlos David Bruque, Lucia Salatino, Vanesa Lotersztein, Sebastián Menazzi, Paola Plazas, Ana Belén Elgoyhen, Viviana Dalamón

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Hearing loss (HL) is the most prevalent sensorineural disorder affecting about 10% of the global population, with more than half due to genetic causes. About 1 in 500-1000 newborns present congenital HL. Most of the patients are non-syndromic with an autosomal recessive mode of inheritance. To date, more than 100 genes are related to HL. Therefore, the Whole-exome sequencing (WES) technique has become a cost-effective alternative approach for molecular diagnosis. Nevertheless, new challenges arise from the detection of novel variants, in particular missense changes, which can lead to a spectrum of genotype-to-phenotype correlations, which is not always straightforward. In this work, we aimed to identify the genetic causes of HL in isolated and familial cases by designing a multistep approach to analyze target genes related to hearing impairment. Moreover, we performed in silico and in vivo analyses in order to further study the effect of some of the novel variants identified in the hair cell function using the zebrafish model. A total of 650 patients were studied by Sanger Sequencing and Gap-PCR in GJB2 and GJB6 genes, respectively, diagnosing 15.5% of sporadic cases and 36% of familial ones. Overall, 50 different sequence variants were detected. Fifty of the undiagnosed patients with moderate HL were tested for deletions in STRC gene by Multiplex ligation-dependent probe amplification technique (MLPA), leading to 6% of diagnosis. After this initial screening, 50 families were selected to be analyzed by WES, achieving diagnosis in 44% of them. Half of the identified variants were novel. A missense variant in MYO6 gene detected in a family with postlingual HL was selected to be further analyzed. A protein modeling with AlphaFold2 software was performed, proving its pathogenic effect. In order to functionally validate this novel variant, a knockdown phenotype rescue assay in zebrafish was carried out. Injection of wild-type MYO6 mRNA in embryos rescued the phenotype, whereas using the mutant MYO6 mRNA (carrying c.2782C>A variant) had no effect. These results strongly suggest the deleterious effect of this variant on the mobility of stereocilia in zebrafish neuromasts, and hence on the auditory system. In the present work, we demonstrated that our algorithm is suitable for the sequential multigenic approach to HL in our cohort. These results highlight the importance of a combined strategy in order to identify candidate variants as well as the in silico and in vivo studies to analyze and prove their pathogenicity and accomplish a better understanding of the mechanisms underlying the physiopathology of the hearing impairment.

Keywords: diagnosis, genetics, hearing loss, in silico analysis, in vivo analysis, WES, zebrafish

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