Search results for: diagnostic testing

Authors: Hossein Rassi, Marjan Moradi Fard, Masoud Houshmand

Abstract:

Background: Cervical cancer is multistep disease that is thought to result from an interaction between genetic background and environmental factors. Human papillomavirus (HPV) infection is the leading risk factor for cervical intraepithelial neoplasia(CIN)and cervical cancer. In other hand, some of p53 and miRNA polymorphism may plays an important role in carcinogenesis. This study attempts to clarify the relation of p53 genotypes and miR-146a rs2910164 polymorphism in cervical lesions. Method: Forty two archival samples with cervical lesion retired from Khatam hospital and 40 sample from healthy persons used as control group. A simple and rapid method was used to detect the simultaneous amplification of the HPV consensus L1 region and HPV-16,-18, -11, -31, 33 and -35 along with the b-globin gene as an internal control. We use Multiplex PCR for detection of P53 and miR-146a rs2910164 genotypes in our lab. Finally, data analysis was performed using the 7 version of the Epi Info(TM) 2012 software and test chi-square(x2) for trend. Results: Cervix lesions were collected from 42 patients with Squamous metaplasia, cervical intraepithelial neoplasia, and cervical carcinoma. Successful DNA extraction was assessed by PCR amplification of b-actin gene (99bp). According to the results, p53 GG genotype and miR-146a rs2910164 CC genotype was significantly associated with increased risk of cervical lesions in the study population. In this study, we detected 13 HPV 18 from 42 cervical cancer. Conclusion: The connection between several SNP polymorphism and human virus papilloma in rare researches were seen. The reason of these differences in researches' findings can result in different kinds of races and geographic situations and also differences in life grooves in every region. The present study provided preliminary evidence that a p53 GG genotype and miR-146a rs2910164 CC genotype may effect cervical cancer risk in the study population, interacting synergistically with HPV 18 genotype. Our results demonstrate that the testing of p53 codon 72 polymorphism genotypes and miR-146a rs2910164 polymorphism genotypes in combination with HPV18 can serve as major risk factors in the early identification of cervical cancers. Furthermore, the results indicate the possibility of primary prevention of cervical cancer by vaccination against HPV18 in Iran.

Keywords: cervical cancer, p53, miR-146a, rs2910164, polymorphism

Procedia PDF Downloads 447

Authors: Jinlai Bian, Zailin Yang, Guanxixi Jiang, Xinzhu Li

Abstract:

The problem of elastic wave propagation in inhomogeneous medium has always been a classic problem. Due to the frequent occurrence of earthquakes, many economic losses and casualties have been caused, therefore, to prevent earthquake damage to people and reduce damage, this paper studies the dynamic response around the circular inclusion in the whole space with inhomogeneous modulus, the inhomogeneity of the medium is reflected in the shear modulus of the medium with the spatial position, and the density is constant, this method can be used to solve the problem of the underground buried pipeline. Stress concentration phenomena are common in aerospace and earthquake engineering, and the dynamic stress concentration factor (DSCF) is one of the main factors leading to material damage, one of the important applications of the theory of elastic dynamics is to determine the stress concentration in the body with discontinuities such as cracks, holes, and inclusions. At present, the methods include wave function expansion method, integral transformation method, integral equation method and so on. Based on the complex function method, the Helmholtz equation with variable coefficients is standardized by using conformal transformation method and wave function expansion method, the displacement and stress fields in the whole space with circular inclusions are solved in the complex coordinate system, the unknown coefficients are solved by using boundary conditions, by comparing with the existing results, the correctness of this method is verified, based on the superiority of the complex variable function theory to the conformal transformation, this method can be extended to study the inclusion problem of arbitrary shapes. By solving the dynamic stress concentration factor around the inclusions, the influence of the inhomogeneous parameters of the medium and the wavenumber ratio of the inclusions to the matrix on the dynamic stress concentration factor is analyzed. The research results can provide some reference value for the evaluation of nondestructive testing (NDT), oil exploration, seismic monitoring, and soil-structure interaction.

Keywords: circular inclusions, complex variable function, dynamic stress concentration factor (DSCF), inhomogeneous medium

Procedia PDF Downloads 113

Authors: Marjan Moradi fard, Hossein Rassi, Masoud Houshmand

Abstract:

Aim: Breast cancer is one of the most common cancers affecting the morbidity and mortality of Iranian women. This disease is a result of collective alterations of oncogenes and tumor suppressor genes. Studies have produced conflicting results concerning the role of p53 codon 72 polymorphism (G>C) and miR-146a rs2910164 polymorphism (G>C) on the risk of several cancers; therefore, a research was performed to estimate the association between the p53 codon 72 polymorphism and miR-146a rs2910164 polymorphism in breast cancer. Methods and Materials: A total of 45 archival breast cancer samples from Khatam hospital and 40 healthy samples were collected. Verification of each cancer reported in a relative was sought through the pathology reports of the hospital records. Then, DNA extracted from all samples by standard methods and p53 codon 72 polymorphism genotypes and miR-146a rs2910164 polymorphism genotypes were analyzed using multiplex PCR. The tubules, mitotic activity, necrosis, polymorphism and grade of breast cancer were staged by Nottingham histological grading and immunohistochemical staining of the sections from the paraffin wax embedded tissues for the expression of ER, PR and p53 was carried out using a standard method. Finally, data analysis was performed using the 7 version of the Epi Info(TM) 2012 software and test chi-square(x2) for trend. Results: Successful DNA extraction was assessed by PCR amplification of b-actin gene (99 bp). According to the results, p53 GG genotype and miR-146a rs2910164 CC genotype was significantly associated with increased risk of breast cancer in the study population. In this study, we established that tumors of p53 GG genotype and miR-146a rs2910164 CC genotype exhibited higher mitotic activity, higher polymorphism, lower necrosis, lower tubules, higher ER- and PR-negatives and lower TP53-positives than the other genotypes. Conclusion: The present study provided preliminary evidence that a p53 GG genotype may effect breast cancer risk in the study population, interacting synergistically with miR-146a rs2910164 CC genotype. Our results demonstrate that the testing of p53 codon 72 polymorphism genotypes and miR-146a rs2910164 polymorphism genotypes in combination with clinical parameters can serve as major risk factors in the early identification of breast cancers.

Keywords: breast cancer, miR-146a rs2910164 polymorphism, p53 codon 72 polymorphism, tumors, pathology reports

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Authors: Nurkhairul Bariyah Baharun, Afzan Adam, Reena Rahayu Md Zin

Abstract:

Tumor microenvironment (TME) in breast cancer is mainly composed of cancer cells, immune cells, and stromal cells. The interaction between cancer cells and their microenvironment plays an important role in tumor development, progression, and treatment response. The TME in breast cancer includes tumor-infiltrating lymphocytes (TILs) that are implicated in killing tumor cells. TILs can be found in tumor stroma (sTILs) and within the tumor (iTILs). TILs in triple negative breast cancer (TNBC) have been demonstrated to have prognostic and potentially predictive value. The international Immune-Oncology Biomarker Working Group (TIL-WG) had developed a guideline focus on the assessment of sTILs using hematoxylin and eosin (H&E)-stained slides. According to the guideline, the pathologists use “eye balling” method on the H&E stained- slide for sTILs assessment. This method has low precision, poor interobserver reproducibility, and is time-consuming for a comprehensive evaluation, besides only counted sTILs in their assessment. The TIL-WG has therefore recommended that any algorithm for computational assessment of TILs utilizing the guidelines provided to overcome the limitations of manual assessment, thus providing highly accurate and reliable TILs detection and classification for reproducible and quantitative measurement. This study is carried out to develop a TNBC digital whole slide image (WSI) dataset from H&E-stained slides and IHC (CD4+ and CD8+) stained slides. TNBC cases were retrieved from the database of the Department of Pathology, Hospital Canselor Tuanku Muhriz (HCTM). TNBC cases diagnosed between the year 2010 and 2021 with no history of other cancer and available block tissue were included in the study (n=58). Tissue blocks were sectioned approximately 4 µm for H&E and IHC stain. The H&E staining was performed according to a well-established protocol. Indirect IHC stain was also performed on the tissue sections using protocol from Diagnostic BioSystems PolyVue™ Plus Kit, USA. The slides were stained with rabbit monoclonal, CD8 antibody (SP16) and Rabbit monoclonal, CD4 antibody (EP204). The selected and quality-checked slides were then scanned using a high-resolution whole slide scanner (Pannoramic DESK II DW- slide scanner) to digitalize the tissue image with a pixel resolution of 20x magnification. A manual TILs (sTILs and iTILs) assessment was then carried out by the appointed pathologist (2 pathologists) for manual TILs scoring from the digital WSIs following the guideline developed by TIL-WG 2014, and the result displayed as the percentage of sTILs and iTILs per mm² stromal and tumour area on the tissue. Following this, we aimed to develop an automated digital image scoring framework that incorporates key elements of manual guidelines (including both sTILs and iTILs) using manually annotated data for robust and objective quantification of TILs in TNBC. From the study, we have developed a digital dataset of TNBC H&E and IHC (CD4+ and CD8+) stained slides. We hope that an automated based scoring method can provide quantitative and interpretable TILs scoring, which correlates with the manual pathologist-derived sTILs and iTILs scoring and thus has potential prognostic implications.

Keywords: automated quantification, digital pathology, triple negative breast cancer, tumour infiltrating lymphocytes

Procedia PDF Downloads 85

Authors: Hossein Rassi, Marjan Moradi fard, Masoud Houshmand

Abstract:

Background: Cervical cancer is multistep disease that is thought to result from an interaction between genetic background and environmental factors. Human Papillomavirus (HPV) infection is the leading risk factor for Cervical Intraepithelial Neoplasia (CIN) and cervical cancer. In other hand, some of p53 and miRNA polymorphism may plays an important role in carcinogenesis. This study attempts to clarify the relation of p53 genotypes and miR-146a rs2910164 polymorphism in cervical lesions. Method: Forty two archival samples with cervical lesion retired from Khatam hospital and 40 sample from healthy persons used as control group. A simple and rapid method was used to detect the simultaneous amplification of the HPV consensus L1 region and HPV-16,-18, -11, -31, 33, and -35 along with the b-globin gene as an internal control. We use Multiplex PCR for detection of P53 and miR-146a rs2910164 genotypes in our lab. Finally, data analysis was performed using the 7 version of the Epi Info(TM) 2012 software and test chi-square(x2) for trend. Results: Cervix lesions were collected from 42 patients with Squamous metaplasia, cervical intraepithelial neoplasia, and cervical carcinoma. Successful DNA extraction was assessed by PCR amplification of b-actin gene (99 bp). According to the results, p53 GG genotype and miR-146a rs2910164 CC genotype was significantly associated with increased risk of cervical lesions in the study population. In this study, we detected 13 HPV 18 from 42 cervical cancer. Conclusion: The connection between several SNP polymorphism and human virus papilloma in rare researches were seen. The reason of these differences in researches' findings can result in different kinds of races and geographic situations and also differences in life grooves in every region. The present study provided preliminary evidence that a p53 GG genotype and miR-146a rs2910164 CC genotype may effect cervical cancer risk in the study population, interacting synergistically with HPV 18 genotype. Our results demonstrate that the testing of p53 codon 72 polymorphism genotypes and miR-146a rs2910164 polymorphism genotypes in combination with HPV18 can serve as major risk factors in the early identification of cervical cancers. Furthermore, the results indicate the possibility of primary prevention of cervical cancer by vaccination against HPV18 in Iran.

Keywords: cervical cancer, miR-146a rs2910164 polymorphism, p53 polymorphism, intraepithelial, neoplasia, HPV

Procedia PDF Downloads 378

Authors: Breanna Macumber, Victor A. Huayamave, Emir A. Vela, Wangdo Kim, Tamara T. Chamber, Esteban Centeno

Abstract:

Spina bifida is a type of neural tube defect that affects the nervous system and can lead to problems such as total leg paralysis. Treatment requires physical therapy and rehabilitation. Robotic exoskeletons have been used for rehabilitation to train muscle movement and assist in injury recovery; however, current models focus on the adult populations and not on the infant population. The proposed framework aims to couple a musculoskeletal infant model with a robotic exoskeleton using vacuum-powered artificial muscles to provide rehabilitation to infants affected by spina bifida. The study that drove the input values for the robotic exoskeleton used motion capture technology to collect data from the spontaneous kicking movement of a 2.4-month-old infant lying supine. OpenSim was used to develop the musculoskeletal model, and Inverse kinematics was used to estimate hip joint angles. A total of 4 kicks (A, B, C, D) were selected, and the selection was based on range, transient response, and stable response. Kicks had at least 5° of range of motion with a smooth transient response and a stable period. The robotic exoskeleton used a Vacuum-Powered Artificial Muscle (VPAM) the structure comprised of cells that were clipped in a collapsed state and unclipped when desired to simulate infant’s age. The artificial muscle works with vacuum pressure. When air is removed, the muscle contracts and when air is added, the muscle relaxes. Bench testing was performed using a 6-month-old infant mannequin. The previously developed exoskeleton worked really well with controlled ranges of motion and frequencies, which are typical of rehabilitation protocols for infants suffering with spina bifida. However, the random kicking motion in this study contained high frequency kicks and was not able to accurately replicate all the investigated kicks. Kick 'A' had a greater error when compared to the other kicks. This study has the potential to advance the infant rehabilitation field.

Keywords: musculoskeletal modeling, soft robotics, rehabilitation, pediatrics

Procedia PDF Downloads 80

Authors: Ayman K. El Essawy, Amal M. Hosny, Hala M. Abu Shady

Abstract:

The rapid detection of TB and drug resistance, both optimizes treatment and improves outcomes. In the current study, respiratory specimens were collected from 155 patients. Conventional susceptibility testing and MIC determination were performed for rifampicin (RIF) and isoniazid (INH). Genotype MTBDRplus assay, which is a molecular genetic assay based on the DNA-STRIP technology and specific gene sequencing with primers for rpoB, KatG, and mab-inhA genes were used to detect mutations associated with resistance to rifampicin and isoniazid. In comparison to other categories, most of rifampicin resistant (61.5%) and isoniazid resistant isolates (47.1%) were from patients relapsed in treatment. The genotypic profile (using Genotype MTBDRplus assay) of multi-drug resistant (MDR) isolates showed missing of katG wild type 1 (WT1) band and appearance of mutation band katG MUT2. For isoniazid mono-resistant isolates, 80% showed katG MUT1, 20% showed katG MUT1, and inhA MUT1, 20% showed only inhA MUT1. Accordingly, 100% of isoniazid resistant strains were detected by this assay. Out of 17 resistant strains, 16 had mutation bands for katG distinguished high resistance to isoniazid. The assay could clearly detect rifampicin resistance among 66.7% of MDR isolates that showed mutation band rpoB MUT3 while 33.3% of them were considered as unknown. One mono-resistant rifampicin isolate did not show rifampicin mutation bands by Genotype MTBDRplus assay, but it showed an unexpected mutation in Codon 531 of rpoB by DNA sequence analysis. Rifampicin resistance in this strain could be associated with a mutation in codon 531 of rpoB (based on molecular sequencing), and Genotype MTBDRplus assay could not detect the associated mutation. If the results of Genotype MTBDRplus assay and sequencing were combined, this strain shows hetero-resistance pattern. Gene sequencing of eight selected isolates, previously tested by Genotype MTBDRplus assay, could detect resistance mutations mainly in codon 315 (katG gene), position -15 in inhA promotes gene for isoniazid resistance and codon 531 (rpoB gene) for rifampicin resistance. Genotyping techniques allow distinguishing between recurrent cases of reinfection or reactivation and supports epidemiological studies.

Keywords: M. tuberculosis, rpoB, KatG, inhA, genotype MTBDRplus

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Authors: Lizel Bertie, Kim Johnston

Abstract:

Parental emotion regulation plays a central role in the socialisation of emotion, especially when teaching young children to cope with negative emotions. Despite evidence which shows non-supportive parental responses to children’s expression of negative emotions has implications for the social and emotional development of the child, few studies have investigated risk factors which impact parental emotion socialisation processes. The current study aimed to explore the extent to which parental stress contributes to both difficulties in parental emotion regulation and non-supportive parental responses to children’s expression of negative emotions. In addition, the study examined whether parental use of expressive suppression as an emotion regulation strategy facilitates the influence of parental stress on non-supportive responses by testing the relations in a mediation model. A sample of 140 Australian adults, who identified as parents with children aged 5 to 10 years, completed an online questionnaire. The measures explored recent symptoms of depression, anxiety, and stress, the use of expressive suppression as an emotion regulation strategy, and hypothetical parental responses to scenarios related to children’s expression of negative emotions. A mediated regression indicated that parents who reported higher levels of stress also reported higher levels of expressive suppression as an emotion regulation strategy and increased use of non-supportive responses in relation to young children’s expression of negative emotions. These findings suggest that parents who experience heightened symptoms of stress are more likely to both suppress their emotions in parent-child interaction and engage in non-supportive responses. Furthermore, higher use of expressive suppression strongly predicted the use of non-supportive responses, despite the presence of parental stress. Contrary to expectation, no indirect effect of stress on non-supportive responses was observed via expressive suppression. The findings from the study suggest that parental stress may become a more salient manifestation of psychological distress in a sub-clinical population of parents while contributing to impaired parental responses. As such, the study offers support for targeting overarching factors such as difficulties in parental emotion regulation and stress management, not only as an intervention for parental psychological distress, but also the detection and prevention of maladaptive parenting practices.

Keywords: emotion regulation, emotion socialisation, expressive suppression, non-supportive responses, parental stress

Procedia PDF Downloads 138

Authors: Reema K. AlEssa, Sahar Alshomer, Abdullah Alfaleh, Sultan ALkhenaizan, Mohammed Albalwi

Abstract:

Ichthyosis is a disorder of abnormal keratinization, characterized by excessive scaling, and consists of more than twenty subtypes varied in severity, mode of inheritance, and the genes involved. There is insufficient data in the literature about the epidemiology and characteristics of ichthyosis locally. Our aim is to identify the histopathological features and genetic profile of ichthyosis. Method: It is an observational retrospective case series study conducted in March 2020, included all patients who were diagnosed with Ichthyosis and confirmed by histological and molecular findings over the last 20 years in King Abdulaziz Medical City (KAMC), Riyadh, Saudi Arabia. Molecular analysis was performed by testing genomic DNA and checking genetic variations using the AmpliSeq panel. All disease-causing variants were checked against HGMD, ClinVar, Genome Aggregation Database (gnomAD), and Exome Aggregation Consortium (ExAC) databases. Result: A total of 60 cases of Ichthyosis were identified with a mean age of 13 ± 9.2. There is an almost equal distribution between female patients 29 (48%) and males 31 (52%). The majority of them were Saudis, 94%. More than half of patients presented with general scaling 33 (55%), followed by dryness and coarse skin 19 (31.6%) and hyperlinearity 5 (8.33%). Family history and history of consanguinity were seen in 26 (43.3% ), 13 (22%), respectively. History of colloidal babies was found in 6 (10%) cases of ichthyosis. The most frequent genes were ALOX12B, ALOXE3, CERS3, CYP4F22, DOLK, FLG2, GJB2, PNPLA1, SLC27A4, SPINK5, STS, SUMF1, TGM1, TGM5, VPS33B. Most frequent variations were detected in CYP4F22 in 16 cases (26.6%) followed by ALOXE3 6 (10%) and STS 6 (10%) then TGM1 5 (8.3) and ALOX12B 5 (8.3). The analysis of molecular genetic identified 23 different genetic variations in the genes of ichthyosis, of which 13 were novel mutations. Homozygous mutations were detected in the majority of ichthyosis cases, 54 (90%), and only 1 case was heterozygous. Few cases, 4 (6.6%) had an unknown type of ichthyosis with a negative genetic result. Conclusion: 13 novel mutations were discovered. Also, about half of ichthyosis patients had a positive history of consanguinity.

Keywords: ichthyosis, genetic profile, molecular characterization, congenital ichthyosis

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Authors: Monica Gonzalez Machorro

Abstract:

Dementia is hard to diagnose because of the lack of early physical symptoms. Early dementia recognition is key to improving the living condition of patients. Speech technology is considered a valuable biomarker for this challenge. Recent works have utilized conventional acoustic features and machine learning methods to detect dementia in speech. BERT-like classifiers have reported the most promising performance. One constraint, nonetheless, is that these studies are either based on human transcripts or on transcripts produced by automatic speech recognition (ASR) systems. This research contribution is to explore a method that does not require transcriptions to detect early Alzheimer’s disease (AD) and mild cognitive impairment (MCI). This is achieved by fine-tuning a pre-trained ASR model for the downstream early AD and MCI tasks. To do so, a subset of the thoroughly studied Pitt Corpus is customized. The subset is balanced for class, age, and gender. Data processing also involves cropping the samples into 10-second segments. For comparison purposes, a baseline model is defined by training and testing a Random Forest with 20 extracted acoustic features using the librosa library implemented in Python. These are: zero-crossing rate, MFCCs, spectral bandwidth, spectral centroid, root mean square, and short-time Fourier transform. The baseline model achieved a 58% accuracy. To fine-tune HuBERT as a classifier, an average pooling strategy is employed to merge the 3D representations from audio into 2D representations, and a linear layer is added. The pre-trained model used is ‘hubert-large-ls960-ft’. Empirically, the number of epochs selected is 5, and the batch size defined is 1. Experiments show that our proposed method reaches a 69% balanced accuracy. This suggests that the linguistic and speech information encoded in the self-supervised ASR-based model is able to learn acoustic cues of AD and MCI.

Keywords: automatic speech recognition, early Alzheimer’s recognition, mild cognitive impairment, speech impairment

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Authors: Sheraz Gul

Abstract:

The requirements for progressing a compound to clinical trials is well established and relies on the results from in-vitro and in-vivo animal tests to indicate that it is likely to be safe and efficacious when testing in humans. The typical data package required will include demonstrating compound safety, toxicity, bioavailability, pharmacodynamics (potential effects of the compound on body systems) and pharmacokinetics (how the compound is potentially absorbed, distributed, metabolised and eliminated after dosing in humans). If the desired criteria are met and the compound meets the clinical Candidate criteria and is deemed worthy of further development, a submission to regulatory bodies such as the US Food & Drug Administration for an exploratory Investigational New Drug Study can be made. The purpose of this study is to collect data to establish that the compound will not expose humans to unreasonable risks when used in limited, early-stage clinical studies in patients or normal volunteer subjects (Phase I). These studies are also designed to determine the metabolism and pharmacologic actions of the drug in humans, the side effects associated with increasing doses, and, if possible, to gain early evidence on their effectiveness. In order to reach the above goals, we have developed a pre-clinical high throughput Absorption, Distribution, Metabolism and Excretion–Toxicity (ADME–Toxicity) panel of assays to identify compounds that are likely to meet the Lead and Candidate compound acceptance criteria. This panel includes solubility studies in a range of biological fluids, cell viability studies in cancer and primary cell-lines, mitochondrial toxicity, off-target effects (across the kinase, protease, histone deacetylase, phosphodiesterase and GPCR protein families), CYP450 inhibition (5 different CYP450 enzymes), CYP450 induction, cardio-toxicity (hERG) and gene-toxicity. This panel of assays has been applied to multiple compound series developed in a number of projects delivering Lead and clinical Candidates and examples from these will be presented.

Keywords: absorption, distribution, metabolism and excretion–toxicity , drug discovery, food and drug administration , pharmacodynamics

Procedia PDF Downloads 152

Authors: Breanna Macumber, Victor A. Huayamave, Emir A. Vela, Wangdo Kim, Tamara T. Chamber, Esteban Centeno

Abstract:

Spina bifida is a type of neural tube defect that affects the nervous system and can lead to problems such as total leg paralysis. Treatment requires physical therapy and rehabilitation. Robotic exoskeletons have been used for rehabilitation to train muscle movement and assist in injury recovery; however, current models focus on the adult populations and not on the infant population. The proposed framework aims to couple a musculoskeletal infant model with a robotic exoskeleton using vacuum-powered artificial muscles to provide rehabilitation to infants affected by spina bifida. The study that drove the input values for the robotic exoskeleton used motion capture technology to collect data from the spontaneous kicking movement of a 2.4-month-old infant lying supine. OpenSim was used to develop the musculoskeletal model, and Inverse kinematics was used to estimate hip joint angles. A total of 4 kicks (A, B, C, D) were selected, and the selection was based on range, transient response, and stable response. Kicks had at least 5° of range of motion with a smooth transient response and a stable period. The robotic exoskeleton used a Vacuum-Powered Artificial Muscle (VPAM) the structure comprised of cells that were clipped in a collapsed state and unclipped when desired to simulate infant’s age. The artificial muscle works with vacuum pressure. When air is removed, the muscle contracts and when air is added, the muscle relaxes. Bench testing was performed using a 6-month-old infant mannequin. The previously developed exoskeleton worked really well with controlled ranges of motion and frequencies, which are typical of rehabilitation protocols for infants suffering with spina bifida. However, the random kicking motion in this study contained high frequency kicks and was not able to accurately replicate all the investigated kicks. Kick 'A' had a greater error when compared to the other kicks. This study has the potential to advance the infant rehabilitation field.

Keywords: musculoskeletal modeling, soft robotics, rehabilitation, pediatrics

Procedia PDF Downloads 49

Authors: Eric Lacoste

Abstract:

Laboratory animals are currently widely used as a model of human pathologies in dermatology such as atopic dermatitis (AD). These models provide a better understanding of the pathophysiology of this complex and multifactorial disease, the discovery of potential new therapeutic targets and the testing of the efficacy of new therapeutics. However, confirmation of the correct development of AD is mainly based on histology from skin biopsies requiring invasive surgery or euthanasia of the animals, plus slicing and staining protocols. However, there are currently accessible imaging technologies such as Optical Coherence Tomography (OCT), which allows non-invasive visualization of the main histological structures of the skin (like stratum corneum, epidermis, and dermis) and assessment of the dynamics of the pathology or efficacy of new treatments. Briefly, female immunocompetent hairless mice (SKH1 strain) were sensitized and challenged topically on back and ears for about 4 weeks. Back skin and ears thickness were measured using calliper at 3 occasions per week in complement to a macroscopic evaluation of atopic dermatitis lesions on back: erythema, scaling and excoriations scoring. In addition, OCT was performed on the back and ears of animals. OCT allows a virtual in-depth section (tomography) of the imaged organ to be made using a laser, a camera and image processing software allowing fast, non-contact and non-denaturing acquisitions of the explored tissues. To perform the imaging sessions, the animals were anesthetized with isoflurane, placed on a support under the OCT for a total examination time of 5 to 10 minutes. The results show a good correlation of the OCT technique with classical HES histology for skin lesions structures such as hyperkeratosis, epidermal hyperplasia, and dermis thickness. This OCT imaging technique can, therefore, be used in live animals at different times for longitudinal evaluation by repeated measurements of lesions in the same animals, in addition to the classical histological evaluation. Furthermore, this original imaging technique speeds up research protocols, reduces the number of animals and refines the use of the laboratory animal.

Keywords: atopic dermatitis, mouse model, oxzolone model, histology, imaging

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Authors: Ricardo Alberto Chiong Zevallos, Eduardo Moraes Rego Reis

Abstract:

Pancreatic adenocarcinoma (PDAC) patients have a less than 10% 5-year survival rate. PDAC has no defined diagnostic and prognostic biomarkers. Gemcitabine is the first-line drug in PDAC and several other cancers. Long non-coding RNAs (lncRNAs) contribute to the tumorigenesis and are potential biomarkers for PDAC. Although lncRNAs aren’t translated into proteins, they have important functions. LncRNAs can decoy or recruit proteins from the epigenetic machinery, act as microRNA sponges, participate in protein translocation through different cellular compartments, and even promote chemoresistance. The chromatin remodeling enzyme EZH2 is a histone methyltransferase that catalyzes the methylation of histone 3 at lysine 27, silencing local expression. EZH2 is ambivalent, it can also activate gene expression independently of its histone methyltransferase activity. EZH2 is overexpressed in several cancers and interacts with lncRNAs, being recruited to a specific locus. EZH2 can be recruited to activate an oncogene or silence a tumor suppressor. The lncRNAs misregulation in cancer can result in the differential recruitment of EZH2 and in a distinct epigenetic landscape, promoting chemoresistance. The relevance of the EZH2-lncRNAs interaction to chemoresistant PDAC was assessed by Real Time quantitative PCR (RT-qPCR) and RNA Immunoprecipitation (RIP) experiments with naïve and gemcitabine-resistant PDAC cells. The expression of several lncRNAs and EZH2 gene targets was evaluated contrasting naïve and resistant cells. Selection of candidate genes was made by bioinformatic analysis and literature curation. Indeed, the resistant cell line showed higher expression of chemoresistant-associated lncRNAs and protein coding genes. RIP detected lncRNAs interacting with EZH2 with varying intensity levels in the cell lines. During RIP, the nuclear fraction of the cells was incubated with an antibody for EZH2 and with magnetic beads. The RNA precipitated with the beads-antibody-EZH2 complex was isolated and reverse transcribed. The presence of candidate lncRNAs was detected by RT-qPCR, and the enrichment was calculated relative to INPUT (total lysate control sample collected before RIP). The enrichment levels varied across the several lncRNAs and cell lines. The EZH2-lncRNA interaction might be responsible for the regulation of chemoresistance-associated genes in multiple cancers. The relevance of the lncRNA-EZH2 interaction to PDAC was assessed by siRNA knockdown of a lncRNA, followed by the analysis of the EZH2 target expression by RT-qPCR. The chromatin immunoprecipitation (ChIP) of EZH2 and H3K27me3 followed by RT-qPCR with primers for EZH2 targets also assess the specificity of the EZH2 recruitment by the lncRNA. This is the first report of the interaction of EZH2 and lncRNAs HOTTIP and PVT1 in chemoresistant PDAC. HOTTIP and PVT1 were described as promoting chemoresistance in several cancers, but the role of EZH2 is not clarified. For the first time, the lncRNA LINC01133 was detected in a chemoresistant cancer. The interaction of EZH2 with LINC02577, LINC00920, LINC00941, and LINC01559 have never been reported in any context. The novel lncRNAs-EZH2 interactions regulate chemoresistant-associated genes in PDAC and might be relevant to other cancers. Therapies targeting EZH2 alone weren’t successful, and a combinatorial approach also targeting the lncRNAs interacting with it might be key to overcome chemoresistance in several cancers.

Keywords: epigenetics, chemoresistance, long non-coding RNAs, pancreatic cancer, histone modification

Procedia PDF Downloads 64

Authors: Hasna Elalaoui Elabdallaoui, Abdelaziz Elfazziki, Mohamed Sadgal

Abstract:

Outlines: The social economy is a moral approach to solidarity applied to the projects’ development. To reconcile economic activity and social equity, crowdfunding is as an alternative means of financing social projects. Several collaborative blockchain platforms exist. It eliminates the need for a central authority or an inconsiderate middleman. Also, the costs for a successful crowdfunding campaign are reduced, since there is no commission to be paid to the intermediary. It improves the transparency of record keeping and delegates authority to authorities who may be prone to corruption. Objectives: The objectives are: to define a software infrastructure for projects’ participatory financing within a social and solidarity economy, allowing transparent, secure, and fair management and to have a financial mechanism that improves financial inclusion. Methodology: The proposed methodology is: crowdfunding platforms literature review, financing mechanisms literature review, requirements analysis and project definition, a business plan, Platform development process and implementation technology, and testing an MVP. Contributions: The solution consists of proposing a new approach to crowdfunding based on Islamic financing, which is the principle of Mousharaka inspired by Islamic financing, which presents a financial innovation that integrates ethics and the social dimension into contemporary banking practices. Conclusion: Crowdfunding platforms need to secure projects and allow only quality projects but also offer a wide range of options to funders. Thus, a framework based on blockchain technology and Islamic financing is proposed to manage this arbitration between quality and quantity of options. The proposed financing system, "Musharaka", is a mode of financing that prohibits interests and uncertainties. The implementation is offered on the secure Ethereum platform as investors sign and initiate transactions for contributions using their digital signature wallet managed by a cryptography algorithm and smart contracts. Our proposal is illustrated by a crop irrigation project in the Marrakech region.

Keywords: social economy, Musharaka, blockchain, smart contract, crowdfunding

Procedia PDF Downloads 53

Authors: Jameelah Omolara Yaqub

Abstract:

One of the main reasons for the existence of central bank is that it is believed that central banks have some influence on private sector decisions which will enable the Central Bank to achieve some of its objectives especially that of stable price and economic growth. By the assumption of the New Keynesian theory that prices are fully flexible in the short run, the central bank can temporarily influence real interest rate and, therefore, have an effect on real output in addition to nominal prices. There is, therefore, the need for the Central Bank to monitor, respond to, and influence private sector decisions appropriately. This thus shows that the Central Bank and the private sector will both affect and be affected by each other implying considerable interdependence between the sectors. The interdependence may be simultaneous or not depending on the level of information, readily available and how sensitive prices are to agents’ expectations about the future. The aim of this paper is, therefore, to determine whether the interdependence between asset prices and monetary policy are simultaneous or not and how important is this relationship. Studies on the effects of monetary policy have largely used VAR models to identify the interdependence but most have found small effects of interaction. Some earlier studies have ignored the possibility of simultaneous interdependence while those that have allowed for simultaneous interdependence used data from developed economies only. This study, therefore, extends the literature by using data from a developing economy where information might not be readily available to influence agents’ expectation. In this study, the direction of relationship among variables of interest will be tested by carrying out the Granger causality test. Thereafter, the interaction between asset prices and monetary policy in Nigeria will be tested. Asset prices will be represented by the NSE index as well as real estate prices while monetary policy will be represented by money supply and the MPR respectively. The VAR model will be used to analyse the relationship between the variables in order to take account of potential simultaneity of interdependence. The study will cover the period between 1980 and 2014 due to data availability. It is believed that the outcome of the research will guide monetary policymakers especially the CBN to effectively influence the private sector decisions and thereby achieve its objectives of price stability and economic growth.

Keywords: asset prices, granger causality, monetary policy rate, Nigeria

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Authors: Philipp Wenger, Michael Beltle, Stefan Tenbohlen, Uwe Riechert

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The integration of renewable energy introduces new challenges to the transmission grid, as the power generation is located far from load centers. The associated necessary long-range power transmission increases the demand for high voltage direct current (HVDC) transmission lines and DC distribution grids. HVDC gas-insulated switchgears (GIS) are considered being a key technology, due to the combination of the DC technology and the long operation experiences of AC-GIS. To ensure long-term reliability of such systems, insulation defects must be detected in an early stage. Operational experience with AC systems has proven evidence, that most failures, which can be attributed to breakdowns of the insulation system, can be detected and identified via partial discharge (PD) measurements beforehand. In AC systems the identification of defects relies on the phase resolved partial discharge pattern (PRPD). Since there is no phase information within DC systems this method cannot be transferred to DC PD diagnostic. Furthermore, the behaviour of e.g. free-moving particles differs significantly at DC: Under the influence of a constant direct electric field, charge carriers can accumulate on particles’ surfaces. As a result, a particle can lift-off, oscillate between the inner conductor and the enclosure or rapidly bounces at just one electrode, which is known as firefly motion. Depending on the motion and the relative position of the particle to the electrodes, broadband electromagnetic PD pulses are emitted, which can be recorded by ultra-high frequency (UHF) measuring methods. PDs are often accompanied by light emissions at the particle’s tip which enables optical detection. This contribution investigates PD characteristics of free moving metallic particles in a commercially available 300 kV SF6-insulated HVDC-GIS. The influences of various defect parameters on the particle motion and the PD characteristic are evaluated experimentally. Several particle geometries, such as cylinder, lamella, spiral and sphere with different length, diameter and weight are determined. The applied DC voltage is increased stepwise from inception voltage up to UDC = ± 400 kV. Different physical detection methods are used simultaneously in a time-synchronized setup. Firstly, the electromagnetic waves emitted by the particle are recorded by an UHF measuring system. Secondly, a photomultiplier tube (PMT) detects light emission with a wavelength in the range of λ = 185…870 nm. Thirdly, a high-speed camera (HSC) tracks the particle’s motion trajectory with high accuracy. Furthermore, an electrically insulated electrode is attached to the grounded enclosure and connected to a current shunt in order to detect low frequency ion currents: The shunt measuring system’s sensitivity is in the range of 10 nA at a measuring bandwidth of bw = DC…1 MHz. Currents of charge carriers, which are generated at the particle’s tip migrate through the gas gap to the electrode and can be recorded by the current shunt. All recorded PD signals are analyzed in order to identify characteristic properties of different particles. This includes e.g. repetition rates and amplitudes of successive pulses, characteristic frequency ranges and detected signal energy of single PD pulses. Concluding, an advanced understanding of underlying physical phenomena particle motion in direct electric field can be derived.

Keywords: current shunt, free moving particles, high-speed imaging, HVDC-GIS, UHF

Procedia PDF Downloads 134

Authors: Naridchaya Aberdour, Joanna Kao, Anne Miller, Timothy Shore, Richard Maher, Zhixin Liu

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Background: COVID-19 has and continues to be a strain on healthcare globally, with the number of patients requiring hospitalization exceeding the level of medical support available in many countries. As chest x-rays are the primary respiratory radiological investigation, the Radiological Assessment of Lung Edema (RALE) score was used to quantify the extent of pulmonary infection on baseline imaging. Assessment of RALE score's reproducibility and associations with clinical outcome parameters were then evaluated to determine implications for patient management and prognosis. Methods: A retrospective study was performed with the inclusion of patients testing positive for COVID-19 on nasopharyngeal swab within a single Local Health District in Sydney, Australia and baseline x-ray imaging acquired between January to June 2020. Two independent Radiologists viewed the studies and calculated the RALE scores. Clinical outcome parameters were collected and statistical analysis was performed to assess RALE score reproducibility and possible associations with clinical outcomes. Results: A total of 78 patients met inclusion criteria with the age range of 4 to 91 years old. RALE score concordance between the two independent Radiologists was excellent (interclass correlation coefficient = 0.93, 95% CI = 0.88-0.95, p<0.005). Binomial logistics regression identified a positive correlation with hospital admission (1.87 OR, 95% CI= 1.3-2.6, p<0.005), oxygen requirement (1.48 OR, 95% CI= 1.2-1.8, p<0.005) and invasive ventilation (1.2 OR, 95% CI= 1.0-1.3, p<0.005) for each 1-point increase in RALE score. For each one year increased in age, there was a negative correlation with recovery (0.05 OR, 95% CI= 0.92-1.0, p<0.01). RALE scores above three were positively associated with hospitalization (Youden Index 0.61, sensitivity 0.73, specificity 0.89) and above six were positively associated with ICU admission (Youden Index 0.67, sensitivity 0.91, specificity 0.78). Conclusion: The RALE score can be used as a surrogate to quantify the extent of COVID-19 infection and has an excellent inter-observer agreement. The RALE score could be used to prognosticate and identify patients at high risk of deterioration. Threshold values may also be applied to predict the likelihood of hospital and ICU admission.

Keywords: chest radiography, coronavirus, COVID-19, RALE score

Procedia PDF Downloads 157

Authors: Vishal Mahale, Jayashree Bijwe, Sujeet K. Sinha

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Range of thermal conductivity (TC) of Friction Materials (FMs) is a critical issue since lower TC leads to accumulation of frictional heat on the working surface, which results in excessive fade while higher TC leads to excessive heat flow towards back-plate resulting in boiling of brake-fluid leading to ‘spongy brakes’. This phenomenon prohibits braking action, which is most undesirable. Therefore, TC of the FMs across the brake pads should not be high while along the brake pad, it should be high. To enhance TC, metals in the forms of powder and fibers are used in the FMs. Apart from TC improvement, metals provide strength and structural integrity to the composites. Due to higher TC Copper (Cu) powder/fiber is a most preferred metallic ingredient in FM industry. However, Cu powders/fibers are responsible for metallic wear debris generation, which has harmful effects on aquatic organisms. Hence to get rid of a problem of metallic wear debris generation and to keep the positive effect of TC improvement, incorporation of Cu fabric in NAO brake-pads can be an innovative solution. Keeping this in view, two realistic multi-ingredient FM composites with identical formulations were developed in the form of brake-pads. Out of which one composite series consisted of a single layer of Cu fabric in the body of brake-pad and designated as C1 while double layer of Cu fabric was incorporated in another brake-pad series with designation of C2. Distance of Cu fabric layer from the back-plate was kept constant for C1 and C2. One more composite (C0) was developed without Cu fabric for the sake of comparison. Developed composites were characterized for physical properties. Tribological performance was evaluated on full scale inertia dynamometer by following JASO C 406 testing standard. It was concluded that Cu fabric successfully improved fade resistance by increasing conductivity of the composite and also showed slight improvement in wear resistance. Worn surfaces of pads and disc were analyzed by SEM and EDAX to study wear mechanism.

Keywords: brake inertia dynamometer, copper fabric, non-asbestos organic (NAO) friction materials, thermal conductivity enhancement

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Authors: L. Vivet, L. Benabou, O. Simon

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With highly demanding applications in the field of power electronics, there is an increasing need to have interconnection materials with properties that can ensure both good mechanical assembly and high thermal/electrical conductivities. So far, lead-free solders have been considered an attractive solution, but recently, sintered joints based on nano-silver paste have been used for die attach and have proved to be a promising solution offering increased performances in high-temperature applications. In this work, the main parameters of the bonding process using silver oxalates are studied, i.e., the heating rate and the bonding pressure mainly. Their effects on both the mechanical and thermal properties of the sintered layer are evaluated following an experimental design. Pairs of copper substrates with gold metallization are assembled through the sintering process to realize the samples that are tested using a micro-traction machine. In addition, the obtained joints are examined through microscopy to identify the important microstructural features in relation to the measured properties. The formation of an intermetallic compound at the junction between the sintered silver layer and the gold metallization deposited on copper is also analyzed. Microscopy analysis exhibits a nanoporous structure of the sintered material. It is found that higher temperature and bonding pressure result in higher densification of the sintered material, with higher thermal conductivity of the joint but less mechanical flexibility to accommodate the thermo-mechanical stresses arising during service. The experimental design allows hence the determination of the optimal process parameters to reach sufficient thermal/mechanical properties for a given application. It is also found that the interphase formed between silver and gold metallization is the location where the fracture occurred after the mechanical testing, suggesting that the inter-diffusion mechanism between the different elements of the assembly leads to the formation of a relatively brittle compound.

Keywords: nanoporous structure, silver oxalate, sintering, mechanical strength, thermal conductivity, microelectronic packaging

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Authors: May Bazzi, Shafik Tokmaj, Younes Saberi, Mats Geijer, Tony Jurkiewicz, Patrik Sund, Anna Bjällmark

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Mobile radiography, employing portable X-ray equipment, has become a routine procedure within hospital settings, with chest X-rays in intensive care units standing out as the most prevalent mobile X-ray examinations. This approach is not limited to hospitals alone, as it extends its benefits to imaging patients in various settings, particularly those too frail to be transported, such as elderly care residents in nursing homes. Moreover, the utility of mobile X-ray isn't confined solely to traditional healthcare recipients; it has proven to be a valuable resource for vulnerable populations, including the homeless, drug users, asylum seekers, and patients with multiple co-morbidities. Mobile X-rays reduce patient stress, minimize costly hospitalizations, and offer cost-effective imaging. While studies confirm its reliability, further research is needed, especially regarding image quality. Recent advancements in lightweight equipment with enhanced battery and detector technology provide the potential for nearly handheld radiography. The main aim of this study was to evaluate a new lightweight mobile X-ray system with two different detectors and compare the image quality with a modern stationary system. Methods: A total of 74 images of the chest (chest anterior-posterior (AP) views and chest lateral views) and pelvic/hip region (AP pelvis views, hip AP views, and hip cross-table lateral views) were acquired on a whole-body phantom (Kyotokagaku, Japan), utilizing varying image parameters. These images were obtained using a stationary system - 18 images (Mediel, Sweden), a mobile X-ray system with a second-generation detector - 28 images (FDR D-EVO II; Fujifilm, Japan) and a mobile X-ray system with a third-generation detector - 28 images (FDR D-EVO III; Fujifilm, Japan). Image quality was assessed by visual grading analysis (VGA), which is a method to measure image quality by assessing the visibility and accurate reproduction of anatomical structures within the images. A total of 33 image criteria were used in the analysis. A panel of two experienced radiologists, two experienced radiographers, and two final-term radiographer students evaluated the image quality on a 5-grade ordinal scale using the software Viewdex 3.0 (Viewer for Digital Evaluation of X-ray images, Sweden). Data were analyzed using visual grading characteristics analysis. The dose was measured by the dose-area product (DAP) reported by the respective systems. Results: The mobile X-ray equipment (both detectors) showed significantly better image quality than the stationary equipment for the pelvis, hip AP and hip cross-table lateral images with AUCVGA-values ranging from 0.64-0.92, while chest images showed mixed results. The number of images rated as having sufficient quality for diagnostic use was significantly higher for mobile X-ray generation 2 and 3 compared with the stationary X-ray system. The DAP values were higher for the stationary compared to the mobile system. Conclusions: The new lightweight radiographic equipment had an image quality at least as good as a fixed system at a lower radiation dose. Future studies should focus on clinical images and consider radiographers' viewpoints for a comprehensive assessment.

Keywords: mobile x-ray, visual grading analysis, radiographer, radiation dose

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Authors: Daniel Puciato, Piotr Oleśniewicz, Julita Markiewicz-Patkowska, Krzysztof Widawski, Michał Rozpara, Władysław Mynarski, Agnieszka Gawlik, Małgorzata Dębska, Soňa Jandová

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Physical activity as a part of people’s everyday life reduces the risk of many diseases, including those induced by lifestyle, e.g. obesity, type 2 diabetes, osteoporosis, coronary heart disease, degenerative arthritis, and certain types of cancer. That refers particularly to professionally active people, including the early senior group working on non-manual positions. The aim of the study is to evaluate the relationship between physical activity and the socio-economic status of non-manual workers from Wroclaw—one of the biggest cities in Poland, a model setting for such investigations in this part of Europe. The crucial problem in the research is to find out the percentage of respondents who meet the health-related recommendations of the World Health Organization (WHO) concerning the volume, frequency, and intensity of physical activity, as well as to establish if the most important socio-economic factors, such as gender, age, education, marital status, per capita income, savings and debt, determine the compliance with the WHO physical activity recommendations. During the research, conducted in 2013, 1,170 people (611 women and 559 men) aged 21–60 years were examined. A diagnostic poll method was applied to collect the data. Physical activity was measured with the use of the short form of the International Physical Activity Questionnaire with extended socio-demographic questions, i.e. concerning gender, age, education, marital status, income, savings or debts. To evaluate the relationship between physical activity and selected socio-economic factors, logistic regression was used (odds ratio statistics). Statistical inference was conducted on the adopted ex ante probability level of p<0.05. The majority of respondents met the volume of physical effort recommended for health benefits. It was particularly noticeable in the case of the examined men. The probability of compliance with the WHO physical activity recommendations was highest for workers aged 21–30 years with secondary or higher education who were single, received highest incomes and had savings. The results indicate the relations between physical activity and socio-economic status in the examined women and men. People with lower socio-economic status (e.g. manual workers) are physically active primarily at work, whereas those better educated and wealthier implement physical effort primarily in their leisure time. Among the investigated subjects, the youngest group of non-manual workers have the best chances to meet the WHO standards of physical activity. The study also confirms that secondary education has a positive effect on the public awareness on the role of physical activity in human life. In general, the analysis of the research indicates that there is a relationship between physical activity and some socio-economic factors of the respondents, such as gender, age, education, marital status, income per capita, and the possession of savings. Although the obtained results cannot be applied for the general population, they show some important trends that will be verified in subsequent studies conducted by the authors of the paper.

Keywords: IPAQ, nonmanual workers, physical activity, socioeconomic factors, WHO

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Authors: Michał Jaśkiewicz

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The relation between walkability, place adherence, social relations and quality of life was explored in a Polish context. A considerable number of studies have suggested that environmental factors may influence the quality of life through indirect pathways. The list of possible psychological mediators includes social relations and identity-related variables. Based on the results of Study 1, local identity is a significant mediator in the relationship between neighbourhood walkability and quality of life. It was assumed that pedestrian-oriented neighbourhoods enable residents to interact and that these spontaneous interactions can help to strengthen a sense of local identity, thus influencing the quality of life. We, therefore, conducted further studies, testing the relationship experimentally in studies 2a and 2b. Participants were exposed to (2a) photos of walkable/non-walkable neighbourhoods or (2b) descriptions of high/low-walkable neighbourhoods. They were then asked to assess the walkability of the neighbourhoods and to evaluate their potential social relations and quality of life in these places. In both studies, social relations with neighbours turned out to be a significant mediator between walkability and quality of life. In Study 3, we implemented the measure of overlapping individual and communal identity (fusion with the neighbourhood) and willingness to collective action as mediators. Living in a walkable neighbourhood was associated with identity fusion with that neighbourhood. Participants who felt more fused expressed greater willingness to engage in collective action with other neighbours. Finally, this willingness was positively related to the quality of life in the city. In Study 4, we used commuting time (an aspect of walkability related to the time that people spend travelling to work) as the independent variable. The results showed that a shorter average daily commuting time was linked to more frequent social interactions in the neighbourhood. Individuals who assessed their social interactions as more frequent expressed a stronger city identification, which was in turn related to quality of life. To sum up, our research replicated and extended previous findings on the association between walkability and well-being measures. We introduced potential mediators of this relationship: social interactions in the neighbourhood and identity-related variables.

Keywords: walkability, quality of life, social relations, analysis of mediation

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Authors: Adriana Haulica

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Powered by Machine Learning, Precise medicine is tailored by now to use genetic and molecular profiling, with the aim of optimizing the therapeutic benefits for cohorts of patients. As the majority of Machine Language algorithms come from heuristics, the outputs have contextual validity. This is not very restrictive in the sense that medicine itself is not an exact science. Meanwhile, the progress made in Molecular Biology, Bioinformatics, Computational Biology, and Precise Medicine, correlated with the huge amount of human biology data and the increase in computational power, opens new healthcare challenges. A more accurate diagnosis is needed along with real-time treatments by processing as much as possible from the available information. The purpose of this paper is to present a deeper vision for the future of Artificial Intelligence in Precise medicine. In fact, actual Machine Learning algorithms use standard mathematical knowledge, mostly Euclidian metrics and standard computation rules. The loss of information arising from the classical methods prevents obtaining 100% evidence on the diagnosis process. To overcome these problems, we introduce MEDICOMPILLS, a new architectural concept tool of information processing in Precise medicine that delivers diagnosis and therapy advice. This tool processes poly-field digital resources: global knowledge related to biomedicine in a direct or indirect manner but also technical databases, Natural Language Processing algorithms, and strong class optimization functions. As the name suggests, the heart of this tool is a compiler. The approach is completely new, tailored for omics and clinical data. Firstly, the intrinsic biological intuition is different from the well-known “a needle in a haystack” approach usually used when Machine Learning algorithms have to process differential genomic or molecular data to find biomarkers. Also, even if the input is seized from various types of data, the working engine inside the MEDICOMPILLS does not search for patterns as an integrative tool. This approach deciphers the biological meaning of input data up to the metabolic and physiologic mechanisms, based on a compiler with grammars issued from bio-algebra-inspired mathematics. It translates input data into bio-semantic units with the help of contextual information iteratively until Bio-Logical operations can be performed on the base of the “common denominator “rule. The rigorousness of MEDICOMPILLS comes from the structure of the contextual information on functions, built to be analogous to mathematical “proofs”. The major impact of this architecture is expressed by the high accuracy of the diagnosis. Detected as a multiple conditions diagnostic, constituted by some main diseases along with unhealthy biological states, this format is highly suitable for therapy proposal and disease prevention. The use of MEDICOMPILLS architecture is highly beneficial for the healthcare industry. The expectation is to generate a strategic trend in Precise medicine, making medicine more like an exact science and reducing the considerable risk of errors in diagnostics and therapies. The tool can be used by pharmaceutical laboratories for the discovery of new cures. It will also contribute to better design of clinical trials and speed them up.

Keywords: bio-semantic units, multiple conditions diagnosis, NLP, omics

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Authors: José Luis Gallizo, Pilar Gargallo, Ramon Saladrigues, Manuel Salvador

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This study offers an exploratory statistical analysis of the persistence of annual profits across a sample of firms from different European Union (EU) countries. To this end, a hierarchical Bayesian dynamic model has been used which enables the annual behaviour of those profits to be broken down into a permanent structural and a transitory component, while also distinguishing between general effects affecting the industry as a whole to which each firm belongs and specific effects affecting each firm in particular. This breakdown enables the relative importance of those fundamental components to be more accurately evaluated by country and sector. Furthermore, Bayesian approach allows for testing different hypotheses about the homogeneity of the behaviour of the above components with respect to the sector and the country where the firm develops its activity. The data analysed come from a sample of 23,293 firms in EU countries selected from the AMADEUS data-base. The period analysed ran from 1999 to 2007 and 21 sectors were analysed, chosen in such a way that there was a sufficiently large number of firms in each country sector combination for the industry effects to be estimated accurately enough for meaningful comparisons to be made by sector and country. The analysis has been conducted by sector and by country from a Bayesian perspective, thus making the study more flexible and realistic since the estimates obtained do not depend on asymptotic results. In general terms, the study finds that, although the industry effects are significant, more important are the firm specific effects. That importance varies depending on the sector or the country in which the firm carries out its activity. The influence of firm effects accounts for around 81% of total variation and display a significantly lower degree of persistence, with adjustment speeds oscillating around 34%. However, this pattern is not homogeneous but depends on the sector and country analysed. Industry effects depends also on sector and country analysed have a more marginal importance, being significantly more persistent, with adjustment speeds oscillating around 7-8% with this degree of persistence being very similar for most of sectors and countries analysed.

Keywords: dynamic models, Bayesian inference, MCMC, abnormal returns, persistence of profits, return on assets

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Authors: Freddy Munzhelele

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Setting: the empirical research has shown that the life cycle theory has an impact on the firms’ financing decisions, particularly the dividend pay-outs. Accordingly, the life cycle theory posits that as a firm matures, it gets to a level and capacity where it distributes more cash as dividends. On the other hand, the young firms prioritise investment opportunities sets and their financing; thus, they pay little or no dividends. The research on firms’ financing decisions also demonstrated, among others, the adoption of trade-off and pecking order theories on the dynamics of firms capital structure. The trade-off theory talks to firms holding a favourable position regarding debt structures particularly as to the cost and benefits thereof; and pecking order is concerned with firms preferring a hierarchical order as to choosing financing sources. The case of life cycle hypothesis explaining the financial managers’ decisions as regards the firms’ capital structure dynamics appears to be an interesting link, yet this link has been neglected in corporate finance research. If this link is to be explored as an empirical research, the financial decision-making alternatives will be enhanced immensely, since no conclusive evidence has been found yet as to the dynamics of capital structure. Aim: the aim of this study is to examine the impact of life cycle theory on the capital structure dynamics trade-off and pecking order theories of firms listed in retail, industrial and mining sectors of the JSE. These sectors are among the key contributors to the GDP in the South African economy. Design and methodology: following the postpositivist research paradigm, the study is quantitative in nature and utilises secondary data obtainable from the financial statements of sampled firm for the period 2010 – 2022. The firms’ financial statements will be extracted from the IRESS database. Since the data will be in panel form, a combination of the static and dynamic panel data estimators will used to analyse data. The overall data analyses will be done using STATA program. Value add: this study directly investigates the link between the life cycle theory and the dynamics of capital structure decisions, particularly the trade-off and pecking order theories.

Keywords: life cycle theory, trade-off theory, pecking order theory, capital structure, JSE listed firms

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Authors: Lancer Scott

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Purpose: High quality clinical disaster medicine requires providers working collaboratively to care for multiple patients in chaotic environments; however, many providers lack adequate training. To address this deficit, we created a competency-based, 5-hour Emergency Preparedness Training (EPT) curriculum using didactics, small-group discussion, and kinetic learning. The goal was to evaluate the effect of a short course on improving provider knowledge, confidence and skills in disaster scenarios. Methods: Diverse groups of medical university students, health care professionals, and community members were enrolled between 2011 and 2014. The course consisted of didactic lectures, small group exercises, and two live, multi-patient mass casualty incident (MCI) scenarios. The outcome measures were based on core competencies and performance objectives developed by a curriculum task force and assessed via trained facilitator observation, pre- and post-testing, and a course evaluation. Results: 708 participants completed were trained between November 2011 and August 2014, including 49.9% physicians, 31.9% medical students, 7.2% nurses, and 11% various other healthcare professions. 100% of participants completed the pre-test and 71.9% completed the post-test, with average correct answers increasing from 39% to 60%. Following didactics, trainees met 73% and 96% of performance objectives for the two small group exercises and 68.5% and 61.1% of performance objectives for the two MCI scenarios. Average trainee self-assessment of both overall knowledge and skill with clinical disasters improved from 33/100 to 74/100 (overall knowledge) and 33/100 to 77/100 (overall skill). The course assessment was completed by 34.3% participants, of whom 91.5% highly recommended the course. Conclusion: A relatively short, intensive EPT course can improve the ability of a diverse group of disaster care providers to respond effectively to mass casualty scenarios.

Keywords: clinical disaster medicine, training, hospital preparedness, surge capacity, education, curriculum, research, performance, training, student, physicians, nurses, health care providers, health care

Procedia PDF Downloads 171

Authors: Hossein Rassi, Marjan Moradi Fard, Masoud Houshmand

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Background: Cervical cancer is multistep disease that is thought to result from an interaction between genetic background and environmental factors. Human papillomavirus (HPV) infection is the leading risk factor for cervical intraepithelial neoplasia (CIN) and cervical cancer. In other hand, some of p53 and miRNA polymorphism may plays an important role in carcinogenesis. This study attempts to clarify the relation of p53 genotypes and miR-146a rs2910164 polymorphism in cervical lesions. Method: Forty two archival samples with cervical lesion retired from Khatam hospital and 40 sample from healthy persons used as control group. A simple and rapid method was used to detect the simultaneous amplification of the HPV consensus L1 region and HPV-16,-18, -11, -31, 33 and -35 along with the b-globin gene as an internal control. We use Multiplex PCR for detection of P53 and miR-146a rs2910164 genotypes in our lab. Finally, data analysis was performed using the 7 version of the Epi Info(TM) 2012 software and test chi-square(x2) for trend. Results: Cervix lesions were collected from 42 patients with Squamous metaplasia, cervical intraepithelial neoplasia, and cervical carcinoma. Successful DNA extraction was assessed by PCR amplification of b-actin gene (99bp). According to the results, p53 GG genotype and miR-146a rs2910164 CC genotype was significantly associated with increased risk of cervical lesions in the study population. In this study, we detected 13 HPV 18 from 42 cervical cancer. Conclusion: The connection between several SNP polymorphism and human virus papilloma in rare researches were seen. The reason of these differences in researches' findings can result in different kinds of races and geographic situations and also differences in life grooves in every region. The present study provided preliminary evidence that a p53 GG genotype and miR-146a rs2910164 CC genotype may effect cervical cancer risk in the study population, interacting synergistically with HPV 18 genotype. Our results demonstrate that the testing of p53 codon 72 polymorphism genotypes and miR-146a rs2910164 polymorphism genotypes in combination with HPV18 can serve as major risk factors in the early identification of cervical cancers. Furthermore, the results indicate the possibility of primary prevention of cervical cancer by vaccination against HPV18 in Iran.

Keywords: cervical cancer, HPV18, p53 codon 72 polymorphism, miR-146a rs2910164 polymorphism

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Authors: Sisaynew Tesfaw Admassu

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The strengthening of timber beams can be necessary for several reasons including the increase of live loads (possible in a historical building for a change of destination of use or upgrading to meet new requirements), the reduction of the resistant cross-sections following deterioration (attacks of biological agents such as fungi, and insects) or traumatic events (fires) and the excess of deflection in the members. The main purpose of strengthening an element is not merely to repair it, but also to prevent and minimize the appearance of future problems. This study did an experimental investigation on the behavior of reference and strengthened solid timber beams. The strengthening materials used in this study were CSM-450 glass fiber and steel materials for both flexural and shear strengthening techniques. Twenty-two solid timber beams of Juniperus procera (TID) species with the dimensions of 60 x 90 x 780 mm were used in the present study. The binding material to bond the strengthening materials with timber was general-purpose resin with Luperox® K10 MEKP catalyst. Three beams were used as control beams (unstrengthen beams) while the remaining nineteen beams were strengthened using the strengthening materials for flexure and shear. All the beams were tested for three points loading to failure by using a Universal Testing Machine, UTM-600kN machine. The experimental results showed that the strengthened beams performed better than the unstrengthen beams. The experimental result of flexural strengthened beams showed that the load-bearing capacity of strengthened beams increased between 16.34 – 42.55%. Four layers of Glass Fiber Reinforced polymer on the tension side of the beams was shown to be the most effective way to enhance load-bearing capacity. The strengthened beams also have an enhancement in their flexural stiffness. The stiffness of flexural strengthened beams was increased between 1.18 – 65.53% as compared to the control beams. The highest increment in stiffness has occurred on beams strengthened using 2x60 mm steel plates. The shear-strengthened beams showed a relatively small amount of performance as compared to flexural-strengthened beams; the reason is that the beams are sufficient for shear. The polyester resin used in the experimental work showed good performance in bonding agents between materials. The resin showed more effectiveness in GFRP materials than steel materials.

Keywords: heritage structures, strengthening, stiffness, adhesive, polyester resin, steel plates

Procedia PDF Downloads 43

Authors: Domenico Palladino, Nicolandrea Calabrese, Francesca Caffari, Giulia Centi, Francesca Margiotta, Giovanni Murano, Laura Ronchetti, Paolo Signoretti, Lisa Volpe, Silvia Di Turi

Abstract:

The aim to achieve a fully decarbonized building stock by 2050 stands as one of the most challenging issues within the spectrum of energy and climate objectives. Numerous strategies are imperative, particularly emphasizing the reduction and optimization of energy demand. Ensuring the high energy performance of buildings emerges as a top priority, with measures aimed at cutting energy consumptions. Concurrently, it is imperative to decrease greenhouse gas emissions by using renewable energy sources for the on-site energy production, thereby striving for an energy balance leading towards zero-emission buildings. Italy's predominant building stock comprises ancient buildings, many of which hold historical significance and are subject to stringent preservation and conservation regulations. Attaining high levels of energy efficiency and reducing CO2 emissions in such buildings poses a considerable challenge, given their unique characteristics and the imperative to adhere to principles of conservation and restoration. Additionally, conducting a meticulous analysis of these buildings' current state is crucial for accurately quantifying their energy performance and predicting the potential impacts of proposed renovation strategies on energy consumption reduction. Within this framework, the paper presents a pilot case in Rome, outlining a methodological approach for the renovation of historic buildings towards achieving Zero Emission Building (ZEB) objective. The building has a mixed function with offices, a conference hall, and an exposition area. The building envelope is made of historical and precious materials used as cladding which must be preserved. A thorough understanding of the building's current condition serves as a prerequisite for analyzing its energy performance. This involves conducting comprehensive archival research, undertaking on-site diagnostic examinations to characterize the building envelope and its systems, and evaluating actual energy usage data derived from energy bills. Energy simulations and audit are the first step in the analysis with the assessment of the energy performance of the actual current state. Subsequently, different renovation scenarios are proposed, encompassing advanced building techniques, to pinpoint the key actions necessary for improving mechanical systems, automation and control systems, and the integration of renewable energy production. These scenarios entail different levels of renovation, ranging from meeting minimum energy performance goals to achieving the highest possible energy efficiency level. The proposed interventions are meticulously analyzed and compared to ascertain the feasibility of attaining the Zero Emission Building objective. In conclusion, the paper provides valuable insights that can be extrapolated to inform a broader approach towards energy-efficient refurbishment of historical buildings that may have limited potential for renovation in their building envelopes. By adopting a methodical and nuanced approach, it is possible to reconcile the imperative of preserving cultural heritage with the pressing need to transition towards a sustainable, low-carbon future.

Keywords: energy conservation and transition, energy efficiency in historical buildings, buildings energy performance, energy retrofitting, zero emission buildings, energy simulation

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