Search results for: efficacy prediction

Authors: Parvesh Singh, Vipan Kumar, Vishu Mehra

Abstract:

Quinoline-4-ones represent an important class of heterocyclic scaffolds that have attracted significant interest due to their various biological and pharmacological activities. This heterocyclic unit also constitutes an integral component in drugs used for the treatment of neurodegenerative diseases, sleep disorders and in antibiotics viz. norfloxacin and ciprofloxacin. The synthetic accessibility and possibility of fictionalization at varied positions in quinoline-4-ones exemplifies an elegant platform for the designing of combinatorial libraries of functionally enriched scaffolds with a range of pharmacological profles. They are also considered to be attractive precursors for the synthesis of medicinally imperative molecules such as non-steroidal androgen receptor antagonists, antimalarial drug Chloroquine and martinellines with antibacterial activity. 2-Aryl-2,3-dihydroquinolin-4(1H)-ones are present in many natural and non-natural compounds and are considered to be the aza-analogs of favanones. The β-lactam class of antibiotics is generally recognized to be a cornerstone of human health care due to the unparalleled clinical efficacy and safety of this type of antibacterial compound. In addition to their biological relevance as potential antibiotics, β-lactams have also acquired a prominent place in organic chemistry as synthons and provide highly efficient routes to a variety of non-protein amino acids, such as oligopeptides, peptidomimetics, nitrogen-heterocycles, as well as biologically active natural and unnatural products of medicinal interest such as indolizidine alkaloids, paclitaxel, docetaxel, taxoids, cyptophycins, lankacidins, etc. A straight forward route toward the synthesis of quinoline-4-ones via the triflic acid assisted Fries rearrangement of N-aryl-βlactams has been reported by Tepe and co-workers. The ring expansion observed in this case was solely attributed to the inherent ring strain in β-lactam ring because -lactam failed to undergo rearrangement under reaction conditions. Theabovementioned protocol has been recently extended by our group for the synthesis of benzo[b]-azocinon-6-ones via a tandem Michael addition–Fries rearrangement of sorbyl anilides as well as for the single-pot synthesis of 2-aryl-quinolin-4(3H)-ones through the Fries rearrangement of 3-dienyl-βlactams. In continuation with our synthetic endeavours with the β-lactam ring and in view of the lack of convenient approaches for the synthesis of C-3 functionalized quinolin-4(1H)-ones, the present work describes the single-pot synthesis of C-3 functionalized quinolin-4(1H)-ones via the trific acid promoted Fries rearrangement of C-3 vinyl/isopropenyl substituted β-lactams. In addition, DFT calculations and MD simulations were performed to investigate the stability profles of synthetic compounds.

Keywords: dihydroquinoline, fries rearrangement, azetidin-2-ones, quinoline-4-ones

Procedia PDF Downloads 235

Authors: Kanduru Lokesh, Venkitasamy Kesavan

Abstract:

The unique structural features of spiro-oxindoles with diverse biological activities have made them privileged structures in new drug discovery. The key structural characteristic of these compounds is the spiro ring fused at the C-3 position of the oxindole core with varied heterocyclic motifs. Structural diversification of heterocyclic scaffolds to synthesize new chemical entities as pharmaceuticals and agrochemicals is one of the important goals of synthetic organic chemists. Nitrogen and oxygen containing heterocycles are by far the most widely occurring privileged structures in medicinal chemistry. The structural complexity and distinct three-dimensional arrangement of functional groups of these privileged structures are generally responsible for their specificity against biological targets. Structurally diverse compound libraries have proved to be valuable assets for drug discovery against challenging biological targets. Thus, identifying a new combination of substituents at C-3 position on oxindole moiety is of great importance in drug discovery to improve the efficiency and efficacy of the drugs. The development of suitable methodology for the synthesis of spiro-oxindole compounds has attracted much interest often in response to the significant biological activity displayed by the both natural and synthetic compounds. So creating structural diversity of oxindole scaffolds is need of the decade and formidable challenge. A general way to improve synthetic efficiency and also to access diversified molecules is through the annulation reactions. Annulation reactions allow the formation of complex compounds starting from simple substrates in a single transformation consisting of several steps in an ecologically and economically favorable way. These observations motivated us to develop the annulation reaction protocol to enable the synthesis of a new class of spiro-oxindole motifs which in turn would enable the enhancement of molecular diversity. As part of our enduring interest in the development of novel, efficient synthetic strategies to enable the synthesis of biologically important oxindole fused spirocarbocyclic systems, We have developed an efficient methodology for the construction of highly functionalized spirocarbocyclic oxindoles through [4+2] annulation of phthalides via Hauser annulation. functionalized spirocarbocyclic oxindoles was accomplished for the first time in the literature using Hauser annulation strategy. The reaction between methyleneindolinones and arylsulfonylphthalides catalyzed by cesium carbonate led to the access of new class of biologically important spiro[indoline-3,2'-naphthalene] derivatives in very good yields. The synthetic utility of the annulated product was further demonstrated by fluorination Using NFSI as a fluorinating agent to furnish corresponding fluorinated product.

Keywords: Hauser-Kraus annulation, spiro carbocyclic oxindoles, oxindole-ester, fluoridation

Procedia PDF Downloads 188

Authors: S. Hussain, C. Grieco, M. Brosnan

Abstract:

Background and Aims: Autism is a complex neurobehavioural disorder, characterised by impairments in the development of language and communication skills. The study involved a state-of-art systematic review, in addition to qualitative data analysis, to establish the evidence for social stories as an intervention strategy for autistic children. An up-to-date review of the use of digital technologies in the delivery of interventions to autistic children was also carried out; to propose the efficacy of digital technologies and the use of social stories to improve intervention outcomes for autistic children. Methods: Two student researchers reviewed a range of randomised control trials and observational studies. The aim of the review was to establish if there was adequate evidence to justify recommending social stories to autistic patients. Students devised their own search strategies to be used across a range of search engines, including Ovid-Medline, Google Scholar and PubMed. Students then critically appraised the generated literature. Additionally, qualitative data obtained from a comprehensive online questionnaire on social stories was also thematically analysed. The thematic analysis was carried out independently by each researcher, using a ‘bottom-up’ approach, meaning contributors read and analysed responses to questions and devised semantic themes from reading the responses to a given question. The researchers then placed each response into a semantic theme or sub-theme. The students then joined to discuss the merging of their theme headings. The Inter-rater reliability (IRR) was calculated before and after theme headings were merged, giving IRR for pre- and post-discussion. Lastly, the thematic analysis was assessed by a third researcher, who is a professor of psychology and the director for the ‘Centre for Applied Autism Research’ at the University of Bath. Results: A review of the literature, as well as thematic analysis of qualitative data found supporting evidence for social story use. The thematic analysis uncovered some interesting themes from the questionnaire responses, relating to the reasons why social stories were used and the factors influencing their effectiveness in each case. However, overall, the evidence for digital technologies interventions was limited, and the literature could not prove a causal link between better intervention outcomes for autistic children and the use of technologies. However, they did offer valid proposed theories for the suitability of digital technologies for autistic children. Conclusions: Overall, the review concluded that there was adequate evidence to justify advising the use of social stories with autistic children. The role of digital technologies is clearly a fast-emerging field and appears to be a promising method of intervention for autistic children; however, it should not yet be considered an evidence-based approach. The students, using this research, developed ideas on social story interventions which aim to help autistic children.

Keywords: autistic children, digital technologies, intervention, social stories

Procedia PDF Downloads 106

Authors: Arindam Chaudhuri

Abstract:

Classification of data has been actively used for most effective and efficient means of conveying knowledge and information to users. The prima face has always been upon techniques for extracting useful knowledge from data such that returns are maximized. With emergence of huge datasets the existing classification techniques often fail to produce desirable results. The challenge lies in analyzing and understanding characteristics of massive data sets by retrieving useful geometric and statistical patterns. We propose a supervised parallel fuzzy rough support vector machine (PFRSVM) for data classification in cloud environment. The classification is performed by PFRSVM using hyperbolic tangent kernel. The fuzzy rough set model takes care of sensitiveness of noisy samples and handles impreciseness in training samples bringing robustness to results. The membership function is function of center and radius of each class in feature space and is represented with kernel. It plays an important role towards sampling the decision surface. The success of PFRSVM is governed by choosing appropriate parameter values. The training samples are either linear or nonlinear separable. The different input points make unique contributions to decision surface. The algorithm is parallelized with a view to reduce training times. The system is built on support vector machine library using Hadoop implementation of MapReduce. The algorithm is tested on large data sets to check its feasibility and convergence. The performance of classifier is also assessed in terms of number of support vectors. The challenges encountered towards implementing big data classification in machine learning frameworks are also discussed. The experiments are done on the cloud environment available at University of Technology and Management, India. The results are illustrated for Gaussian RBF and Bayesian kernels. The effect of variability in prediction and generalization of PFRSVM is examined with respect to values of parameter C. It effectively resolves outliers’ effects, imbalance and overlapping class problems, normalizes to unseen data and relaxes dependency between features and labels. The average classification accuracy for PFRSVM is better than other classifiers for both Gaussian RBF and Bayesian kernels. The experimental results on both synthetic and real data sets clearly demonstrate the superiority of the proposed technique.

Keywords: FRSVM, Hadoop, MapReduce, PFRSVM

Procedia PDF Downloads 477

Authors: N. C. van der Merwe, J. Oosthuizen, M. F. Makhetha, J. Adams, B. K. Dajee, S-R. Schneider

Abstract:

Women representing high-risk breast cancer families, who tested negative for pathogenic mutations in BRCA1 and BRCA2, are four times more likely to develop breast cancer compared to women in the general population. Sequencing of genes involved in genomic stability and DNA repair led to the identification of novel contributors to familial breast cancer risk. These include BLM and PALB2. Bloom's syndrome is a rare homozygous autosomal recessive chromosomal instability disorder with a high incidence of various types of neoplasia and is associated with breast cancer when in a heterozygous state. PALB2, on the other hand, binds to BRCA2 and together, they partake actively in DNA damage repair. Archived DNA samples of 66 BRCA1/2 negative high-risk breast cancer patients were retrospectively selected based on the presence of an extensive family history of the disease ( > 3 affecteds per family). All coding regions and splice-site boundaries of both genes were screened using High-Resolution Melting Analysis. Samples exhibiting variation were bi-directionally automated Sanger sequenced. The clinical significance of each variant was assessed using various in silico and splice site prediction algorithms. Comprehensive screening identified a total of 11 BLM and 26 PALB2 variants. The variants detected ranged from global to rare and included three novel mutations. Three BLM and two PALB2 likely pathogenic mutations were identified that could account for the disease in these extensive breast cancer families in the absence of BRCA mutations (BLM c.11T > A, p.V4D; BLM c.2603C > T, p.P868L; BLM c.3961G > A, p.V1321I; PALB2 c.421C > T, p.Gln141Ter; PALB2 c.508A > T, p.Arg170Ter). Conclusion: The study confirmed the contribution of pathogenic mutations in BLM and PALB2 to the familial breast cancer burden in South Africa. It explained the presence of the disease in 7.5% of the BRCA1/2 negative families with an extensive family history of breast cancer. Segregation analysis will be performed to confirm the clinical impact of these mutations for each of these families. These results justify the inclusion of both these genes in a comprehensive breast and ovarian next generation sequencing cancer panel and should be screened simultaneously with BRCA1 and BRCA2 as it might explain a significant percentage of familial breast and ovarian cancer in South Africa.

Keywords: Bloom Syndrome, familial breast cancer, PALB2, South Africa

Procedia PDF Downloads 214

Authors: D. N. Kambrekar, S. B. Jagginavar, J. Aruna

Abstract:

Grape stem borer, Celosterna scrabrator is an important production constraint in grapes in India. Hitherto this pest was a severe menace only on the aged and unmanaged fields but during the recent past it has also started damaging the newly established fields. In India, since Karnataka, Andra Pradesh, Tamil Nadu and Maharashtra are the major grape production states, the incidence of stem borer is also restricted and severe in these states. The grubs of the beetle bore in to the main stem and even the branches, which affect the translocation of nutrients to the areal parts of the plant. Since, the grubs bore inside the stem, the chewed material along with its excreta is discharged outside the holes and the frass is found on the ground just below the bored holes. The portion of vines above the damaged part has a sticky appearance. The leaves become pale yellow which looks like a deficiency of micronutrients. The leaves ultimately dry and drop down. The status of the incidence of the grape stem borer in different grape growing districts of Northern Karnataka was carried out during three years. In each taluka five locations were surveyed for the incidence of grape stem borer. Further, the experiment on management of stem borer was carried out in the grape gardens of Vijayapur districts under farmers field during three years. Stem borer infested plants that show live holes were selected per treatments and it was replicated three times. Live and dead holes observed during pre-treatment were closely monitored and only plants with live holes were selected and tagged. Different doses of chlorantraniliprole 0.4% GR were incorporated into the soil around the vine basins near root zone surrounded to trunk region by removing soils up to 5-10 cm with a peripheral distance of 1 to 1.5 feet from the main trunk where feeder roots are present. Irrigation was followed after application of insecticide for proper incorporation of the test chemical. The results indicated that there was sever to moderate incidence of the stem borer in all the grape growing districts of northern Karnataka. Maximum incidence was recorded in Belagavi (11 holes per vine) and minimum was in Gadag district (8.5 holes per vine). The investigations carried out to study the efficacy of chlorantraniliprole on grape stem borer for successive three years under farmers field indicated that chlorantraniliprole @ 15g/vine applied just near the active root zone of the plant followed by irrigation has successfully managed the pest. The insecticide has translocated to all the parts of the plants and thereby stopped the activity of the pest which has resulted in to better growth of the plant and higher berry yield compared to other treatments under investigation. Thus, chlorantraniliprole 0.4 GR @ 15g/vine can be effective means in managing the stem borer.

Keywords: chlorantraniliprole, grape stem borer, Celosterna scrabrator, management

Procedia PDF Downloads 429

Authors: Fouzia Khanam, Tridib Chowdhury, Belal Hossain, Sajedur Rahman, Mahfuzar Rahman

Abstract:

Introduction: Over the last decades, the world has achieved a noticeable success in preventing malaria. Nevertheless, malaria, a vector-borne infectious disease, remains a major public health burden globally as well as in Bangladesh. To achieve the goal of eliminating malaria, BRAC, a leading organization of Bangladesh in collaboration with government, is distributing free LLIN to the 13 endemic districts of the country. The study was conducted with the aim of assessing the gap between coverage, access, and utilization of LLIN among the people of the 13 malaria endemic districts of Bangladesh. Methods: This baseline study employed a community cross-sectional design triangulated with qualitative methods to measure households’ ownership, access and use of 13 endemic districts. A multistage cluster random sampling was employed for the quantitative part and for qualitative part a purposive sampling strategy was done. Thus present analysis included 2640 households encompassing a total of 14475 populations. Data were collected using a pre-tested structured questionnaire through one on one face-to-face interview with respondents. All analyses were performed using STATA (Version 13.0). For the qualitative part participant observation, in-depth interview, focus group discussion, key informant interview and informal interview was done to gather the contextual data. Findings: According to our study, 99.8% of households possessed at least one-bed net in both study areas. 77.4% households possessed at least two LLIN and 43.2% households had access to LLIN for all the members. So the gap between coverage and access is 34%. 91.8% people in the 13 districts and 95.1% in Chittagong Hill Tracts areas reported having had slept under a bed net the night before interviewed. And despite the relatively low access, in 77.8% of households, all the members were used the LLIN the previous night. This higher utilization compared to access might be due to the increased awareness among the community people regarding LLIN uses. However, among those people with sufficient access to LLIN, 6% of them still did not use the LLIN which reflects the behavioral failure that needs to be addressed. The major reasons for not using LLIN, identified by both qualitative and quantitative findings, were insufficient access, sleeping or living outside the home, migration, perceived low efficacy of LLIN, fear of physical side effects or feeling uncomfortable. Conclusion: Given that LLIN access and use was a bit short of the targets, it conveys important messages to the malaria control program. Targeting specific population segments and groups for achieving expected LLIN coverage is very crucial. And also, addressing behavior failure by well-designed behavioral change interventions is mandatory.

Keywords: long lasting insecticide net, malaria, malaria control programme, World Health Organisation

Procedia PDF Downloads 170

Authors: Narendra Akhadkar, Philippe Delcambre

Abstract:

In power protection and control products, assembly process variations due to the individual parts manufactured from single or multi-cavity tooling is a major problem. The dimensional and geometrical variations on the individual parts, in the form of manufacturing tolerances and assembly tolerances, are sources of clearance in the kinematic joints, polarization effect in the joints, and tolerance stack-up. All these variations adversely affect the quality of product, functionality, cost, and time-to-market. Variation simulation analysis may be used in the early product design stage to predict such uncertainties. Usually, variations exist in both manufacturing processes and materials. In the tolerance analysis, the effect of the dimensional and geometrical variations of the individual parts on the functional characteristics (conditions) of the final assembled products are studied. A functional characteristic of the product may be affected by a set of interrelated dimensions (functional parameters) that usually form a geometrical closure in a 3D chain. In power protection and control products, the prerequisite is: when a fault occurs in the electrical network, the product must respond quickly to react and break the circuit to clear the fault. Usually, the response time is in milliseconds. Any failure in clearing the fault may result in severe damage to the equipment or network, and human safety is at stake. In this article, we have investigated two important functional characteristics that are associated with the robust performance of the product. It is demonstrated that the experimental data obtained at the Schneider Electric Laboratory prove the very good prediction capabilities of the variation simulation performed using CETOL (tolerance analysis software) in an industrial context. Especially, this study allows design engineers to better understand the critical parts in the product that needs to be manufactured with good, capable tolerances. On the contrary, some parts are not critical for the functional characteristics (conditions) of the product and may lead to some reduction of the manufacturing cost, ensuring robust performance. The capable tolerancing is one of the most important aspects in product and manufacturing process design. In the case of miniature circuit breaker (MCB), the product's quality and its robustness are mainly impacted by two aspects: (1) allocation of design tolerances between the components of a mechanical assembly and (2) manufacturing tolerances in the intermediate machining steps of component fabrication.

Keywords: geometrical variation, product robustness, tolerance analysis, variation simulation

Procedia PDF Downloads 148

Authors: Waleed Omri

Abstract:

With the growth of the small business sector in emerging markets, developing a better understanding of what drives 'day-to-day' entrepreneurial activities has become an important issue for academicians and practitioners. Innovation, as an entrepreneurial behavior, revolves around individuals who creatively engage in new organizational efforts. In a similar vein, the innovation behaviors and processes at the organizational member level are central to any corporate entrepreneurship strategy. Despite the broadly acknowledged importance of entrepreneurship and innovation at the individual level in the establishment of successful ventures, the literature lacks evidence on how entrepreneurs can effectively harness their skills and knowledge in the workplace. The existing literature illustrates that religion can impact the day-to-day work behavior of entrepreneurs, managers, and employees. Religious beliefs and practices could affect daily entrepreneurial activities by fostering mental abilities and traits such as creativity, intelligence, and self-efficacy. In the present study, we define religious capital as a set of personal and intangible resources, skills, and competencies that emanate from an individual’s religious values, beliefs, practices, and experiences and may be used to increase the quality of economic activities. Religious beliefs and practices give individuals a religious satisfaction, which can lead them to perform better in the workplace. In addition, religious ethics and practices have been linked to various positive employee outcomes in terms of organizational change, job satisfaction, and entrepreneurial intensity. As investigations of their consequences beyond direct task performance are still scarce, we explore if religious capital plays a role in entrepreneurs’ innovative behavior. In sum, this study explores the determinants of individual entrepreneurial behavior by investigating the relationship between religious capital and entrepreneurs’ innovative behavior in the context of small businesses. To further explain and clarify the religious capital-innovative behavior link, the present study proposes a model to examine the mediating role of entrepreneurial creativity. We use both Islamic work ethics (IWE) and Islamic religious practices (IRP) to measure Islamic religious capital. We use structural equation modeling with a robust maximum likelihood estimation to analyze data gathered from 289 Tunisian small businesses and to explore the relationships among the above-described variables. In line with the theory of planned behavior, only religious work ethics are found to increase the innovative behavior of small businesses’ owner-managers. Our findings also clearly demonstrate that the connection between religious capital-related variables and innovative behavior is better understood if the influence of entrepreneurial creativity, as a mediating variable of the aforementioned relationship, is taken into account. By incorporating both religious capital and entrepreneurial creativity into the innovative behavior analysis, this study provides several important practical implications for promoting innovation process in small businesses.

Keywords: entrepreneurial behavior, small business, religion, creativity

Procedia PDF Downloads 228

Authors: Hanwei Gao, Louis Jezequel, Eric Cabrol, Bernard Vitry

Abstract:

The chassis system is composed of complex elements that take up all the loads from the tire-ground contact area and thus it plays an important role in numerous specifications such as durability, comfort, crash, etc. During the development of new vehicle projects in Renault, durability validation is always the main focus while deployment of comfort comes later in the project. Therefore, sometimes design choices have to be reconsidered because of the natural incompatibility between these two specifications. Besides, robustness is also an important point of concern as it is related to manufacturing costs as well as the performance after the ageing of components like shock absorbers. In this paper an approach is proposed aiming to realize a multi-objective optimization between chassis endurance and comfort while taking the random factors into consideration. The adaptive-sparse polynomial chaos expansion method (PCE) with Chebyshev polynomial series has been applied to predict responses’ uncertainty intervals of a system according to its uncertain-but-bounded parameters. The approach can be divided into three steps. First an initial design of experiments is realized to build the response surfaces which represent statistically a black-box system. Secondly within several iterations an optimum set is proposed and validated which will form a Pareto front. At the same time the robustness of each response, served as additional objectives, is calculated from the pre-defined parameter intervals and the response surfaces obtained in the first step. Finally an inverse strategy is carried out to determine the parameters’ tolerance combination with a maximally acceptable degradation of the responses in terms of manufacturing costs. A quarter car model has been tested as an example by applying the road excitations from the actual road measurements for both endurance and comfort calculations. One indicator based on the Basquin’s law is defined to compare the global chassis durability of different parameter settings. Another indicator related to comfort is obtained from the vertical acceleration of the sprung mass. An optimum set with best robustness has been finally obtained and the reference tests prove a good robustness prediction of Chebyshev PCE method. This example demonstrates the effectiveness and reliability of the approach, in particular its ability to save computational costs for a complex system.

Keywords: chassis durability, Chebyshev polynomials, multi-objective optimization, polynomial chaos expansion, ride comfort, robust design

Procedia PDF Downloads 142

Authors: Mustafa Alhamdi

Abstract:

Industrial application to classify gamma rays and neutron events is investigated in this study using deep machine learning. The identification using a convolutional neural network and recursive neural network showed a significant improvement in predication accuracy in a variety of applications. The ability to identify the isotope type and activity from spectral information depends on feature extraction methods, followed by classification. The features extracted from the spectrum profiles try to find patterns and relationships to present the actual spectrum energy in low dimensional space. Increasing the level of separation between classes in feature space improves the possibility to enhance classification accuracy. The nonlinear nature to extract features by neural network contains a variety of transformation and mathematical optimization, while principal component analysis depends on linear transformations to extract features and subsequently improve the classification accuracy. In this paper, the isotope spectrum information has been preprocessed by finding the frequencies components relative to time and using them as a training dataset. Fourier transform implementation to extract frequencies component has been optimized by a suitable windowing function. Training and validation samples of different isotope profiles interacted with CdTe crystal have been simulated using Geant4. The readout electronic noise has been simulated by optimizing the mean and variance of normal distribution. Ensemble learning by combing voting of many models managed to improve the classification accuracy of neural networks. The ability to discriminate gamma and neutron events in a single predication approach using deep machine learning has shown high accuracy using deep learning. The paper findings show the ability to improve the classification accuracy by applying the spectrogram preprocessing stage to the gamma and neutron spectrums of different isotopes. Tuning deep machine learning models by hyperparameter optimization of neural network models enhanced the separation in the latent space and provided the ability to extend the number of detected isotopes in the training database. Ensemble learning contributed significantly to improve the final prediction.

Keywords: machine learning, nuclear physics, Monte Carlo simulation, noise estimation, feature extraction, classification

Procedia PDF Downloads 135

Authors: Peter J. Fusco, Dave M. Mathew, Chris Mathew, Kenneth H. Levy, Kathryn S. Varghese, Stephanie Salazar-Restrepo, Serena M. Mathew, Sofia Khaja, Eamon Vega, Mia Polizzi, Alyssa Mullane, Adham Ahmed

Abstract:

Background: Laparoscopic (LS) removal of neuroblastomas in children has been reported to offer favorable outcomes compared to the conventional open thoracotomy (OT) procedure. Critical perioperative measures such as blood loss, operative time, length of stay, and time to postoperative chemotherapy have all supported laparoscopic use rather than its more invasive counterpart. Herein, a pairwise meta-analysis was performed comparing perioperative outcomes between LS and OT in thoracoabdominal neuroblastoma cases. Methods: A comprehensive literature search was performed on PubMed, Ovid EMBASE, and Scopus databases to identify studies comparing the outcomes of pediatric patients with thoracoabdominal neuroblastomas undergoing resection via OT or LS. After deduplication, 4,227 studies were identified and subjected to initial title screening with exclusion and inclusion criteria to ensure relevance. When studies contained overlapping cohorts, only the larger series were included. Primary outcomes include estimated blood loss (EBL), hospital length of stay (LOS), and mortality, while secondary outcomes were tumor recurrence, post-operative complications, and operation length. The “meta” and “metafor” packages were used in R, version 4.0.2, to pool risk ratios (RR) or standardized mean differences (SMD) in addition to their 95% confidence intervals in the random effects model via the Mantel-Haenszel method. Heterogeneity between studies was assessed using the I² test, while publication bias was assessed via funnel plot. Results: The pooled analysis included 209 patients from 5 studies (141 OT, 68 LS). Of the included studies, 2 originated from the United States, 1 from Toronto, 1 from China, and 1was from a Japanese center. Mean age between study cohorts ranged from 2.4 to 5.3 years old, with female patients occupying between 30.8% to 50% of the study populations. No statistically significant difference was found between the two groups for LOS (SMD -1.02; p=0.083), mortality (RR 0.30; p=0.251), recurrence(RR 0.31; p=0.162), post-operative complications (RR 0.73; p=0.732), or operation length (SMD -0.07; p=0.648). Of note, LS appeared to be protective in the analysis for EBL, although it did not reach statistical significance (SMD -0.4174; p= 0.051). Conclusion: Despite promising literature assessing LS removal of pediatric neuroblastomas, results showed it was non-superior to OT for any explored perioperative outcomes. Given the limited comparative data on the subject, it is evident that randomized trials are necessary to further the efficacy of the conclusions reached.

Keywords: laparoscopy, neuroblastoma, thoracoabdominal, thoracotomy

Procedia PDF Downloads 117

Authors: Bellinda R. Chinowawa

Abstract:

As part of a wider strategy to stifle civil society, Governments routinely resort to judicial harassment through the use of civil and criminal to impugn the integrity of human rights defenders and that of perceived political opponents. This phenomenon is rife in militarised or autocratic regimes where there is no tolerance for dissenting voices. Zimbabwe, ostensibly a presidential republic founded on the values of transparency, equality, freedom, is characterised by brutal suppression of perceived political opponents and those who assert their basic human rights. This is done through a wide range of tactics including unlawful arrests and detention, torture and other cruel, inhuman degrading treatment and enforced disappearances. Professionals including, journalists and doctors are similarly not spared from state attack. For human rights defenders, the most widely used tool of repression is that of judicial harassment where the judicial system is used to persecute them. This can include the levying of criminal charges, civil lawsuits and unnecessary administrative proceedings. Charges preferred against range from petty offences such as criminal nuisance to more serious charges of terrorism and subverting a constitutional government. Additionally, government sponsored individuals and organisations file strategic lawsuits with pecuniary implications order to intimidate and silence critics and engender self-censorship. Some HRDs are convicted and sentenced to prison terms, despite not being criminals in a true sense. While others are acquitted judicial harassment diverts energy and resources away from their human rights work. Through a consideration of statistical data reported by human rights organisations and face to face interviews with a cross section of human rights defenders, the article will map the incidence of judicial harassment in Zimbabwe. The article will consider the multi-level sociological and contextual factors which influence the Government of Zimbabwe to have easy recourse to criminal law and the debilitating effect of these actions on HRDs. These factors include the breakdown of the rule of law resulting in state capture of the judiciary, the proven efficacy of judicial harassment from colonial times to date, and the lack of an adequate redress mechanism at international level. By mapping the use of the judiciary as a tool of repression, from the inception of modern day Zimbabwe to date, it is hoped that HRDs will realise that they are part of a greater community of activists throughout the ages and should emboldened in the realisation that it is an age old tactic used by fallen regimes which should not deter them from calling for accountability.

Keywords: autocratic regime, colonial legacy, judicial harassment, human rights defenders

Procedia PDF Downloads 223

Authors: Pavitra Sharma, Anuradha Singh, Nupur Mathur

Abstract:

There exist more than 100 trillion bacteria in the digestive system of human-beings. Such bacteria are referred to as gut microbiota. Gut microbiota comprises around 75% of our immune system. The bacteria that comprise the gut microbiota are unique to every individual and their composition keeps changing with time owing to factors such as the host’s age, diet, genes, environment, and external medication. Of these factors, the variable easiest to control is one’s diet. By modulating one’s diet, one can ensure an optimal composition of the gut microbiota yielding several health benefits. Prebiotics and probiotics are two compounds that have been considered as viable options to modulate the host’s diet. Prebiotics are basically plant products that support the growth of good bacteria in the host’s gut. Examples include garden asparagus, aloe vera etc. Probiotics are living microorganisms that exist in our intestines and play an integral role in promoting digestive health and supporting our immune system in general. Examples include yogurt, kimchi, kombucha etc. In the context of modulating the host’s diet, the key attribute of prebiotics is that they support the growth of probiotics. By developing the right combination of prebiotics and probiotics, food products or supplements can be created to enhance the host’s health. An effective combination of prebiotics and probiotics that yields health benefits to the host is referred to as synbiotics. Synbiotics comprise of an optimal proportion of prebiotics and probiotics, their application benefits the host’s health more than the application of prebiotics and probiotics used in isolation. When applied to food supplements, synbiotics preserve the beneficial probiotic bacteria during storage period and during the bacteria’s passage through the intestinal tract. When applied to the gastrointestinal tract, the composition of the synbiotics assumes paramount importance. Reason being that for synbiotics to be effective in the gastrointestinal tract, the chosen probiotic must be able to survive in the stomach’s acidic environment and manifest tolerance towards bile and pancreatic secretions. Further, not every prebiotic stimulates the growth of a particular probiotic. The prebiotic chosen should be one that not only maintains 2 balance in the host’s digestive system, but also provides the required nutrition to probiotics. Hence in each application of synbiotics, the prebiotic-probiotic combination needs to be carefully selected. Once the combination is finalized, the exact proportion of prebiotics and probiotics to be used needs to be considered. When determining this proportion, only that amount of a prebiotic should be used that activates metabolism of the required number of probiotics. It was observed that while probiotics are active is both the small and large intestine, the effect of prebiotics is observed primarily in the large intestine. Hence in the host’s small intestine, synbiotics are likely to have the maximum efficacy. In small intestine, prebiotics not only assist in the growth of probiotics, but they also enable probiotics to exhibit a higher tolerance to pH levels, oxygenation, and intestinal temperature

Keywords: microbiota, probiotics, prebiotics, synbiotics

Procedia PDF Downloads 121

Authors: Nur Fareza Mustapha

Abstract:

Solutions to policy problems need to be curated to the local context, taking into account the trajectory of the local development path to ensure its efficacy. For Kuala Lumpur, rapid urbanization and migration into the city for the past few decades have increased the demand for housing to accommodate a growing urban population. As a critical factor affecting housing affordability, land supply constraints have been attributed to intensifying market pressures, which grew in tandem with the demands of urban development, along with existing institutional constraints in the governance of land. While demand-side pressures are inevitable given the fixed supply of land, supply-side constraints in regulations distort markets and if addressed inappropriately, may lead to mistargeted policy interventions. Given Malaysia’s historical development, regulatory barriers for land may originate from the British colonial period, when many aspects of the current laws governing tenure were introduced and formalized, and henceforth, became engrained in the system. This research undertakes a postcolonial institutional analysis approach to uncover the causal mechanism driving the evolution of land tenure systems in post-colonial Kuala Lumpur. It seeks to determine the sources of these shifts, focusing on the incentives and bargaining positions of actors during periods of institutional flux/change. It aims to construct a conceptual framework to further this understanding and to elucidate how this historical trajectory affects current access to urban land markets for housing. Archival analysis is used to outline and analyse the evolution of land tenure systems in Kuala Lumpur while stakeholder interviews are used to analyse its impact on the current urban land market, with a particular focus on the provision of and access to affordable housing in the city. Preliminary findings indicate that many aspects of the laws governing tenure that were introduced and formalized during the British colonial period have endured until the present day. Customary rules of tenure were displaced by rules following a European tradition, which found legitimacy through a misguided interpretation of local laws regarding the ownership of land. Colonial notions of race and its binary view of native vs. non-natives have also persisted in the construction and implementation of current legislation regarding land tenure. More concrete findings from this study will generate a more nuanced understanding of the regulatory land supply constraints in Kuala Lumpur, taking into account both the long and short term spatial and temporal processes that affect how these rules are created, implemented and enforced.

Keywords: colonial discourse, historical institutionalism, housing, land policy, post-colonial city

Procedia PDF Downloads 114

Authors: E. Menga, S. Hernandez

Abstract:

Finite Element Models (FEMs) are widely used in order to study and predict the dynamic properties of structures and usually, the prediction can be obtained with much more accuracy in the case of a single component than in the case of assemblies. Especially for structural dynamics studies, in the low and middle frequency range, most complex FEMs can be seen as assemblies made by linear components joined together at interfaces. From a modelling and computational point of view, these types of joints can be seen as localized sources of stiffness and damping and can be modelled as lumped spring/damper elements, most of time, characterized by nonlinear constitutive laws. On the other side, most of FE programs are able to run nonlinear analysis in time-domain. They treat the whole structure as nonlinear, even if there is one nonlinear degree of freedom (DOF) out of thousands of linear ones, making the analysis unnecessarily expensive from a computational point of view. In this work, a methodology in order to obtain the nonlinear frequency response of structures, whose nonlinearities can be considered as localized sources, is presented. The work extends the well-known Structural Dynamic Modification Method (SDMM) to a nonlinear set of modifications, and allows getting the Nonlinear Frequency Response Functions (NLFRFs), through an ‘updating’ process of the Linear Frequency Response Functions (LFRFs). A brief summary of the analytical concepts is given, starting from the linear formulation and understanding what the implications of the nonlinear one, are. The response of the system is formulated in both: time and frequency domain. First the Modal Database is extracted and the linear response is calculated. Secondly the nonlinear response is obtained thru the NL SDMM, by updating the underlying linear behavior of the system. The methodology, implemented in MATLAB, has been successfully applied to estimate the nonlinear frequency response of two systems. The first one is a two DOFs spring-mass-damper system, and the second example takes into account a full aircraft FE Model. In spite of the different levels of complexity, both examples show the reliability and effectiveness of the method. The results highlight a feasible and robust procedure, which allows a quick estimation of the effect of localized nonlinearities on the dynamic behavior. The method is particularly powerful when most of the FE Model can be considered as acting linearly and the nonlinear behavior is restricted to few degrees of freedom. The procedure is very attractive from a computational point of view because the FEM needs to be run just once, which allows faster nonlinear sensitivity analysis and easier implementation of optimization procedures for the calibration of nonlinear models.

Keywords: frequency response, nonlinear dynamics, structural dynamic modification, softening effect, rubber

Procedia PDF Downloads 254

Authors: Markus Rütten, Olaf Wünsch

Abstract:

Non-Newtonian fluid properties can change the flow behaviour significantly, its prediction is more difficult when thermal effects come into play. Hence, the focal point of this work is the wake flow behind a heated circular cylinder in the laminar vortex shedding regime for thermo-viscous shear thinning fluids. In the case of isothermal flows of Newtonian fluids the vortex shedding regime is characterised by a distinct Reynolds number and an associated Strouhal number. In the case of thermo-viscous shear thinning fluids the flow regime can significantly change in dependence of the temperature of the viscous wall of the cylinder. The Reynolds number alters locally and, consequentially, the Strouhal number globally. In the present CFD study the temperature dependence of the Reynolds and Strouhal number is investigated for the flow of a Carreau fluid around a heated cylinder. The temperature dependence of the fluid viscosity has been modelled by applying the standard Williams-Landel-Ferry (WLF) equation. In the present simulation campaign thermal boundary conditions have been varied over a wide range in order to derive a relation between dimensionless heat transfer, Reynolds and Strouhal number. Together with the shear thinning due to the high shear rates close to the cylinder wall this leads to a significant decrease of viscosity of three orders of magnitude in the nearfield of the cylinder and a reduction of two orders of magnitude in the wake field. Yet the shear thinning effect is able to change the flow topology: a complex K´arm´an vortex street occurs, also revealing distinct characteristic frequencies associated with the dominant and sub-dominant vortices. Heating up the cylinder wall leads to a delayed flow separation and narrower wake flow, giving lesser space for the sequence of counter-rotating vortices. This spatial limitation does not only reduce the amplitude of the oscillating wake flow it also shifts the dominant frequency to higher frequencies, furthermore it damps higher harmonics. Eventually the locally heated wake flow smears out. Eventually, the CFD simulation results of the systematically varied thermal flow parameter study have been used to describe a relation for the main characteristic order parameters.

Keywords: heat transfer, thermo-viscous fluids, shear thinning, vortex shedding

Procedia PDF Downloads 286

Authors: Taylan Kabbani, Ekrem Duman

Abstract:

The design of adaptive systems that take advantage of financial markets while reducing the risk can bring more stagnant wealth into the global market. However, most efforts made to generate successful deals in trading financial assets rely on Supervised Learning (SL), which suffered from various limitations. Deep Reinforcement Learning (DRL) offers to solve these drawbacks of SL approaches by combining the financial assets price "prediction" step and the "allocation" step of the portfolio in one unified process to produce fully autonomous systems capable of interacting with its environment to make optimal decisions through trial and error. In this paper, a continuous action space approach is adopted to give the trading agent the ability to gradually adjust the portfolio's positions with each time step (dynamically re-allocate investments), resulting in better agent-environment interaction and faster convergence of the learning process. In addition, the approach supports the managing of a portfolio with several assets instead of a single one. This work represents a novel DRL model to generate profitable trades in the stock market, effectively overcoming the limitations of supervised learning approaches. We formulate the trading problem, or what is referred to as The Agent Environment as Partially observed Markov Decision Process (POMDP) model, considering the constraints imposed by the stock market, such as liquidity and transaction costs. More specifically, we design an environment that simulates the real-world trading process by augmenting the state representation with ten different technical indicators and sentiment analysis of news articles for each stock. We then solve the formulated POMDP problem using the Twin Delayed Deep Deterministic Policy Gradient (TD3) algorithm, which can learn policies in high-dimensional and continuous action spaces like those typically found in the stock market environment. From the point of view of stock market forecasting and the intelligent decision-making mechanism, this paper demonstrates the superiority of deep reinforcement learning in financial markets over other types of machine learning such as supervised learning and proves its credibility and advantages of strategic decision-making.

Keywords: the stock market, deep reinforcement learning, MDP, twin delayed deep deterministic policy gradient, sentiment analysis, technical indicators, autonomous agent

Procedia PDF Downloads 166

Authors: Ella Tyuryumina, Alexey Neznanov

Abstract:

This study is an attempt to obtain reliable data on the natural history of breast cancer growth. We analyze the opportunities for using classical mathematical models (exponential and logistic tumor growth models, Gompertz and von Bertalanffy tumor growth models) to try to describe growth of the primary tumor and the secondary distant metastases of human breast cancer. The research aim is to improve predicting accuracy of breast cancer progression using an original mathematical model referred to CoMPaS and corresponding software. We are interested in: 1) modelling the whole natural history of the primary tumor and the secondary distant metastases; 2) developing adequate and precise CoMPaS which reflects relations between the primary tumor and the secondary distant metastases; 3) analyzing the CoMPaS scope of application; 4) implementing the model as a software tool. The foundation of the CoMPaS is the exponential tumor growth model, which is described by determinate nonlinear and linear equations. The CoMPaS corresponds to TNM classification. It allows to calculate different growth periods of the primary tumor and the secondary distant metastases: 1) ‘non-visible period’ for the primary tumor; 2) ‘non-visible period’ for the secondary distant metastases; 3) ‘visible period’ for the secondary distant metastases. The CoMPaS is validated on clinical data of 10-years and 15-years survival depending on the tumor stage and diameter of the primary tumor. The new predictive tool: 1) is a solid foundation to develop future studies of breast cancer growth models; 2) does not require any expensive diagnostic tests; 3) is the first predictor which makes forecast using only current patient data, the others are based on the additional statistical data. The CoMPaS model and predictive software: a) fit to clinical trials data; b) detect different growth periods of the primary tumor and the secondary distant metastases; c) make forecast of the period of the secondary distant metastases appearance; d) have higher average prediction accuracy than the other tools; e) can improve forecasts on survival of breast cancer and facilitate optimization of diagnostic tests. The following are calculated by CoMPaS: the number of doublings for ‘non-visible’ and ‘visible’ growth period of the secondary distant metastases; tumor volume doubling time (days) for ‘non-visible’ and ‘visible’ growth period of the secondary distant metastases. The CoMPaS enables, for the first time, to predict ‘whole natural history’ of the primary tumor and the secondary distant metastases growth on each stage (pT1, pT2, pT3, pT4) relying only on the primary tumor sizes. Summarizing: a) CoMPaS describes correctly the primary tumor growth of IA, IIA, IIB, IIIB (T1-4N0M0) stages without metastases in lymph nodes (N0); b) facilitates the understanding of the appearance period and inception of the secondary distant metastases.

Keywords: breast cancer, exponential growth model, mathematical model, metastases in lymph nodes, primary tumor, survival

Procedia PDF Downloads 329

Authors: Ani Demetrashvili

Abstract:

As online learning continues to reshape the landscape of education, questions arise regarding its efficacy for diverse learning styles, particularly for visual learners. This abstract delves into the impact of online learning on visual learners, exploring how digital mediums influence their educational experience and how educational platforms can be optimized to cater to their needs. Visual learners comprise a significant portion of the student population, characterized by their preference for visual aids such as diagrams, charts, and videos to comprehend and retain information. Traditional classroom settings often struggle to accommodate these learners adequately, relying heavily on auditory and written forms of instruction. The advent of online learning presents both opportunities and challenges in addressing the needs of visual learners. Online learning platforms offer a plethora of multimedia resources, including interactive simulations, virtual labs, and video lectures, which align closely with the preferences of visual learners. These platforms have the potential to enhance engagement, comprehension, and retention by presenting information in visually stimulating formats. However, the effectiveness of online learning for visual learners hinges on various factors, including the design of learning materials, user interface, and instructional strategies. Research into the impact of online learning on visual learners encompasses a multidisciplinary approach, drawing from fields such as cognitive psychology, education, and human-computer interaction. Studies employ qualitative and quantitative methods to assess visual learners' preferences, cognitive processes, and learning outcomes in online environments. Surveys, interviews, and observational studies provide insights into learners' preferences for specific types of multimedia content and interactive features. Cognitive tasks, such as memory recall and concept mapping, shed light on the cognitive mechanisms underlying learning in digital settings. Eye-tracking studies offer valuable data on attentional patterns and information processing during online learning activities. The findings from research on the impact of online learning on visual learners have significant implications for educational practice and technology design. Educators and instructional designers can use insights from this research to create more engaging and effective learning materials for visual learners. Strategies such as incorporating visual cues, providing interactive activities, and scaffolding complex concepts with multimedia resources can enhance the learning experience for visual learners in online environments. Moreover, online learning platforms can leverage the findings to improve their user interface and features, making them more accessible and inclusive for visual learners. Customization options, adaptive learning algorithms, and personalized recommendations based on learners' preferences and performance can enhance the usability and effectiveness of online platforms for visual learners.

Keywords: online learning, visual learners, digital education, technology in learning

Procedia PDF Downloads 18

Authors: Md. Fazlul Karim, Ashik Sharfaraz, Aysha Ferdoushi

Abstract:

Background: Computational medicinal chemistry approaches are used for designing and identifying new drug-like molecules, predicting properties and pharmacological activities, and optimizing lead compounds in drug development. SIRT7, a nicotinamide adenine dinucleotide (NAD+)-dependent deacylase which regulates aging, is an emerging target for cancer therapy with mounting evidence that SIRT7 downregulation plays important roles in reversing cancer phenotypes and suppressing tumor growth. Activation or altered expression of SIRT7 is associated with the progression and invasion of various cancers, including liver, breast, gastric, prostate, and non-small cell lung cancer. Objectives: The goal of this work was to identify potent and selective bioactive candidate inhibitors of SIRT7 by in silico screening of small molecule compounds obtained from Nigella sativa (N. sativa). Methods: SIRT7 structure was retrieved from The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB), and its active site was identified using CASTp and metaPocket. Molecular docking simulation was performed with PyRx 0.8 virtual screening software. Drug-likeness properties were tested using SwissADME and pkCSM. In silico toxicity was evaluated by Osiris Property Explorer. Bioactivity was predicted by Molinspiration software. Antitumor activity was screened for Prediction of Activity Spectra for Substances (PASS) using Way2Drug web server. Molecular dynamics (MD) simulation was carried out by Desmond v3.6 package. Results: A total of 159 bioactive compounds from the N. Sativa were screened against the SIRT7 enzyme. Five bioactive compounds: chrysin (CID:5281607), pinocembrin (CID:68071), nigellidine (CID:136828302), nigellicine (CID:11402337), and epicatechin (CID:72276) were identified as potent SIRT7 anti-cancer candidates after docking score evaluation and applying Lipinski's Rule of Five. Finally, MD simulation identified Chrysin as the top SIRT7 anti-cancer candidate molecule. Conclusion: Chrysin, which shows a potential inhibitory effect against SIRT7, can act as a possible anti-cancer drug candidate. This inhibitor warrants further evaluation to check its pharmacokinetics and pharmacodynamics properties both in vitro and in vivo.

Keywords: SIRT7, antitumor, molecular docking, molecular dynamics simulation

Procedia PDF Downloads 55

Authors: Christian Ihwiwhu, Nnamdi Obioha, Udeme John, Edward Bobade, Oghenerunor Bekibele, Adedeji Awujoola, Ibi-Ada Itotoi

Abstract:

Understanding the complexity in the distribution of hydrocarbon in a simple structure with flow baffles and connectivity issues is critical in targeting and developing the remaining pay in a mature asset. Subtle facies changes (heterogeneity) can have a drastic impact on reservoir fluids movement, and this can be crucial to identifying sweet spots in mature fields. This study aims to evaluate selected reservoirs in Ovhor Field, Niger Delta, Nigeria, with the objective of optimising production from the field by targeting undeveloped oil reserves, bypassed pay, and gaining an improved understanding of the selected reservoirs to increase the company’s reservoir limits. The task at the Ovhor field is complicated by poor stratigraphic seismic resolution over the field. 3-D geological (sedimentology and stratigraphy) interpretation, use of results from quantitative interpretation, and proper understanding of production data have been used in recognizing flow baffles and undeveloped compartments in the field. The full field 3-D model has been constructed in such a way as to capture heterogeneities and the various compartments in the field to aid the proper simulation of fluid flow in the field for future production prediction, proper history matching and design of good trajectories to adequately target undeveloped oil in the field. Reservoir property models (porosity, permeability, and net-to-gross) have been constructed by biasing log interpreted properties to a defined environment of deposition model whose interpretation captures the heterogeneities expected in the studied reservoirs. At least, two scenarios have been modelled for most of the studied reservoirs to capture the range of uncertainties we are dealing with. The total original oil in-place volume for the four reservoirs studied is 157 MMstb. The cumulative oil and gas production from the selected reservoirs are 67.64 MMstb and 9.76 Bscf respectively, with current production rate of about 7035 bopd and 4.38 MMscf/d (as at 31/08/2019). Dynamic simulation and production forecast on the 4 reservoirs gave an undeveloped reserve of about 3.82 MMstb from two (2) identified oil restoration activities. These activities include side-tracking and re-perforation of existing wells. This integrated approach led to the identification of bypassed oil in some areas of the selected reservoirs and an improved understanding of the studied reservoirs. New wells have/are being drilled now to test the results of our studies, and the results are very confirmatory and satisfying.

Keywords: facies, flow baffle, bypassed pay, heterogeneities, history matching, reservoir limit

Procedia PDF Downloads 114

Authors: Diane Ghanem, Oscar Covarrubias, Michael Raad, Dawn LaPorte, Babar Shafiq

Abstract:

Introduction: Standardized exams have long been considered a cornerstone in measuring cognitive competency and academic achievement. Their fixed nature and predetermined scoring methods offer a consistent yardstick for gauging intellectual acumen across diverse demographics. Consequently, the performance of artificial intelligence (AI) in this context presents a rich, yet unexplored terrain for quantifying AI's understanding of complex cognitive tasks and simulating human-like problem-solving skills. Publicly available AI language models such as ChatGPT have demonstrated utility in text generation and even problem-solving when provided with clear instructions. Amidst this transformative shift, the aim of this study is to assess ChatGPT’s performance on the orthopaedic surgery in-training examination (OITE). Methods: All 213 OITE 2021 web-based questions were retrieved from the AAOS-ResStudy website. Two independent reviewers copied and pasted the questions and response options into ChatGPT Plus (version 4.0) and recorded the generated answers. All media-containing questions were flagged and carefully examined. Twelve OITE media-containing questions that relied purely on images (clinical pictures, radiographs, MRIs, CT scans) and could not be rationalized from the clinical presentation were excluded. Cohen’s Kappa coefficient was used to examine the agreement of ChatGPT-generated responses between reviewers. Descriptive statistics were used to summarize the performance (% correct) of ChatGPT Plus. The 2021 norm table was used to compare ChatGPT Plus’ performance on the OITE to national orthopaedic surgery residents in that same year. Results: A total of 201 were evaluated by ChatGPT Plus. Excellent agreement was observed between raters for the 201 ChatGPT-generated responses, with a Cohen’s Kappa coefficient of 0.947. 45.8% (92/201) were media-containing questions. ChatGPT had an average overall score of 61.2% (123/201). Its score was 64.2% (70/109) on non-media questions. When compared to the performance of all national orthopaedic surgery residents in 2021, ChatGPT Plus performed at the level of an average PGY3. Discussion: ChatGPT Plus is able to pass the OITE with a satisfactory overall score of 61.2%, ranking at the level of third-year orthopaedic surgery residents. More importantly, it provided logical reasoning and justifications that may help residents grasp evidence-based information and improve their understanding of OITE cases and general orthopaedic principles. With further improvements, AI language models, such as ChatGPT, may become valuable interactive learning tools in resident education, although further studies are still needed to examine their efficacy and impact on long-term learning and OITE/ABOS performance.

Keywords: artificial intelligence, ChatGPT, orthopaedic in-training examination, OITE, orthopedic surgery, standardized testing

Procedia PDF Downloads 69

Authors: Delphine Morales, Florian Lombart, Agathe Truchot, Pauline Maire, Pascale Vigneron, Antoine Galmiche, Catherine Lok, Muriel Vayssade

Abstract:

Targeted therapy molecules are used as a first-line treatment for metastatic melanoma with B-Raf mutation. Nevertheless, these molecules can cause side effects to patients and are efficient on 50 to 60 % of them. Indeed, melanoma cell sensitivity to targeted therapy molecules is dependent on tumor microenvironment (cell-cell and cell-extracellular matrix interactions). To better unravel factors modulating cell sensitivity to B-Raf inhibitor, we have developed and compared several melanoma models: from metastatic melanoma cells cultured as monolayer (2D) to a co-culture in a 3D dermal equivalent. Cell response was studied in different melanoma cell lines such as SK-MEL-28 (mutant B-Raf (V600E), sensitive to Vemurafenib), SK-MEL-3 (mutant B-Raf (V600E), resistant to Vemurafenib) and a primary culture of dermal human fibroblasts (HDFn). Assays have initially been performed in a monolayer cell culture (2D), then a second time on a 3D dermal equivalent (dermal human fibroblasts embedded in a collagen gel). All cell lines were treated with Vemurafenib (a B-Raf inhibitor) for 48 hours at various concentrations. Cell sensitivity to treatment was assessed under various aspects: Cell proliferation (cell counting, EdU incorporation, MTS assay), MAPK signaling pathway analysis (Western-Blotting), Apoptosis (TUNEL), Cytokine release (IL-6, IL-1α, HGF, TGF-β, TNF-α) upon Vemurafenib treatment (ELISA) and histology for 3D models. In 2D configuration, the inhibitory effect of Vemurafenib on cell proliferation was confirmed on SK-MEL-28 cells (IC50=0.5 µM), and not on the SK-MEL-3 cell line. No apoptotic signal was detected in SK-MEL-28-treated cells, suggesting a cytostatic effect of the Vemurafenib rather than a cytotoxic one. The inhibition of SK-MEL-28 cell proliferation upon treatment was correlated with a strong expression decrease of phosphorylated proteins involved in the MAPK pathway (ERK, MEK, and AKT/PKB). Vemurafenib (from 5 µM to 10 µM) also slowed down HDFn proliferation, whatever cell culture configuration (monolayer or 3D dermal equivalent). SK-MEL-28 cells cultured in the dermal equivalent were still sensitive to high Vemurafenib concentrations. To better characterize all cell population impacts (melanoma cells, dermal fibroblasts) on Vemurafenib efficacy, cytokine release is being studied in 2D and 3D models. We have successfully developed and validated a relevant 3D model, mimicking cutaneous metastatic melanoma and tumor microenvironment. This 3D melanoma model will become more complex by adding a third cell population, keratinocytes, allowing us to characterize the epidermis influence on the melanoma cell sensitivity to Vemurafenib. In the long run, the establishment of more relevant 3D melanoma models with patients’ cells might be useful for personalized therapy development. The authors would like to thank the Picardie region and the European Regional Development Fund (ERDF) 2014/2020 for the funding of this work and Oise committee of "La ligue contre le cancer".

Keywords: 3D human skin model, melanoma, tissue engineering, vemurafenib efficiency

Procedia PDF Downloads 288

Authors: Sandra Smart-Akande, Chaminda Hewage, Imtiaz Khan, Thanuja Mallikarachchi

Abstract:

According to UK police-recorded data, there has been a substantial increase in knife-related crime and youth violence in the UK since 2014 particularly in the London boroughs. These crime rates are disproportionally distributed across London with the majority of these crimes occurring in the highly deprived areas of London and among young people aged 11 to 24 with large discrepancies across ethnicity, age, gender and borough of residence. Comprehensive studies and literature have identified risk factors associated with a knife carrying among youth to be Adverse Childhood Experience (ACEs), poor mental health, school or social exclusion, drug dealing, drug using, victim of violent crime, bullying, peer pressure or gang involvement, just to mention a few. ACEs are potentially traumatic events that occur in childhood, this can be experiences or stressful events in the early life of a child and can lead to an increased risk of damaging health or social outcomes in the latter life of the individual. Research has shown that children or youths involved in youth violence have had childhood experience characterised by disproportionate adverse childhood experiences and substantial literature link ACEs to be associated with criminal or delinquent behavior. ACEs are commonly grouped by researchers into: Abuse (Physical, Verbal, Sexual), Neglect (Physical, Emotional) and Household adversities (Mental Illness, Incarcerated relative, Domestic violence, Parental Separation or Bereavement). To the author's best knowledge, no study to date has investigated how household mental health (mental health of a parent or mental health of a child) and domestic violence (domestic violence on a parent or domestic violence on a child) is related to knife homicides across the local authorities areas of London. This study seeks to address the gap by examining a large sample of data from the London Metropolitan Police Force and Characteristics of Children in Need data from the UK Department for Education. The aim of this review is to identify and synthesise evidence from data and a range of literature to identify the relationship between adverse childhood experiences and youth violence in the UK. Understanding the link between ACEs and future outcomes can support preventative action.

Keywords: adverse childhood experiences, domestic violence, mental health, youth violence, prediction analysis, London knife crime

Procedia PDF Downloads 102

Authors: Alexis Polanco Jr, Tsai Lu Liu

Abstract:

Research on digital assessment for deaf and hard of hearing (DHH) students is negligible. Part of this stems from the DHH assessment design existing at the intersection of the emergent disciplines of usability, accessibility, and child-computer interaction (CCI). While these disciplines have some prevailing guidelines —e.g. in user experience design (UXD), there is Jacob Nielsen’s 10 Usability Heuristics (Nielsen-10); for accessibility, there are the Web Content Accessibility Guidelines (WCAG) & the Principles of Universal Design (PUD)— this research was unable to uncover a unified set of guidelines. Given that digital assessments have lasting implications for the funding and shaping of U.S. school districts, it is vital that cross-disciplinary guidelines emerge. As a result, this research seeks to provide a framework by which these disciplines can share knowledge. The framework entails a process of asking subject-matter experts (SMEs) and design & development professionals to self-describe their fields of expertise, how their work might serve DHH students, and to expose any incongruence between their ideal process and what is permissible at their workplace. This research used two rounds of mixed methods. The first round consisted of structured interviews with SMEs in usability, accessibility, CCI, and DHH education. These practitioners were not designers by trade but were revealed to use designerly work processes. In addition to asking these SMEs about their field of expertise, work process, etc., these SMEs were asked to comment about whether they believed Nielsen-10 and/or PUD were sufficient for designing products for middle-school DHH students. This first round of interviews revealed that Nielsen-10 and PUD were, at best, a starting point for creating middle-school DHH design guidelines or, at worst insufficient. The second round of interviews followed a semi-structured interview methodology. The SMEs who were interviewed in the first round were asked open-ended follow-up questions about their semantic understanding of guidelines— going from the most general sense down to the level of design guidelines for DHH middle school students. Designers and developers who were never interviewed previously were asked the same questions that the SMEs had been asked across both rounds of interviews. In terms of the research goals: it was confirmed that the design of digital assessments for DHH students is inherently cross-disciplinary. Unexpectedly, 1) guidelines did not emerge from the interviews conducted in this study, and 2) the principles of Nielsen-10 and PUD were deemed to be less relevant than expected. Given the prevalence of Nielsen-10 in UXD curricula across academia and certificate programs, this poses a risk to the efficacy of DHH assessments designed by UX designers. Furthermore, the following findings emerged: A) deep collaboration between the disciplines of usability, accessibility, and CCI is low to non-existent; B) there are no universally agreed-upon guidelines for designing digital assessments for DHH middle school students; C) these disciplines are structured academically and professionally in such a way that practitioners may not know to reach out to other disciplines. For example, accessibility teams at large organizations do not have designers and accessibility specialists on the same team.

Keywords: deaf, hard of hearing, design, guidelines, education, assessment

Procedia PDF Downloads 55

Authors: I. C. Orabueze, A. A. Amudalat, S. A. Adesegun, A. A. Usman

Abstract:

Dental and associated oral diseases are increasingly affecting a considerable portion of the population and are considered some of the major causes of tooth loss, discomfort, mouth odor and loss of confidence. This study focused on the ethnobotanical survey of medicinal plants used in oral therapy and evaluation of the antimicrobial activities of methanolic extracts of two selected plants from the survey for their efficacy against dental microorganisms. The ethnobotanical survey was carried out in six herbal markets in Lagos State, Nigeria by oral interviewing and information obtained from an old family manually complied herbal medication book. Methanolic extracts of Olax subscorpioidea (stem bark) and Bridelia ferruginea (stem bark) were assayed for their antimicrobial activities against clinical oral isolates (Aspergillus fumigatus, Candida albicans, Streptococcus spp, Staphylococcus aureus, Lactobacillus acidophilus and Pseudomonas aeruginosa). In vitro microbial technique (agar well diffusion method and minimum inhibitory concentration (MIC) assay) were employed for the assay. Chlorhexidine gluconate was used as the reference drug for comparison with the extract results. And the preliminary phytochemical screening of the constituents of the plants were done. The ethnobotanical survey produced plants (28) of diverse family. Different parts of plants (seed, fruit, leaf, root, bark) were mentioned but 60% mentioned were either the stem or the bark. O. subscorpioidea showed considerable antifungal activity with zone of inhibition ranging from 2.650 – 2.000 cm against Aspergillus fumigatus but no such encouraging inhibitory activity was observed in the other assayed organisms. B. ferruginea showed antibacterial sensitivity against Streptococcus spp, Staphylococcus aureus, Lactobacillus acidophilus and Pseudomonas aeruginosa with zone of inhibitions ranging from 3.400 - 2.500, 2.250 - 1.600, 2.700 - 1.950, 2.225 – 1.525 cm respectively. The minimum inhibitory concentration of O. subscorpioidea against Aspergillus fumigatus was 51.2 mg ml-1 while that of B. ferruginea against Streptococcus spp was 0.1mg ml-1 and for Staphylococcus aureus, Lactobacillus acidophilus and Pseudomonas aeruginosa were 25.6 mg ml-1. A phytochemical analysis reveals the presence of alkaloids, saponins, cardiac glycoside, tannins, phenols and terpenoids in both plants, with steroids only in B. ferruginea. No toxicity was observed among mice given the two methanolic extracts (1000 mg Kg-1) after 21 days. The barks of both plants exhibited antimicrobial properties against periodontal diseases causing organisms assayed, thus up-holding their folkloric use in oral disorder management. Further research could be done viewing these extracts as combination therapy, checking for possible synergistic value in toothpaste and oral rinse formulations for reducing oral bacterial flora and fungi load.

Keywords: antimicrobial activities, Bridelia ferruginea, dental disinfection, methanolic extract, Olax subscorpioidea, ethnobotanical survey

Procedia PDF Downloads 228

Authors: Jui Chen Wu, Ming Yi Hsu

Abstract:

Background and Purpose: Shift work of nursing staff is inevitable in hospital to provide continuing medical care. However, shift work is considered as a health hazard that may cause physical and psychological problems. Serious workplace fatigue of nursing shift work might impact on family, social and work life, moreover, causes serious reduction of quality of medical care, or even malpractice. This study aims to explore relationships among nursing staff’s shift, workplace fatigue and quality of working life. Method: Structured questionnaires were used in this study to explore relationships among shift work, workplace fatigue and quality of working life in nursing staffs. We recruited 590 nursing staffs in different Community Teaching hospitals in Taiwan. Data analysed by descriptive statistics, single sample t-test, single factor analysis, Pearson correlation coefficient and hierarchical regression, etc. Results: The overall workplace fatigue score is 50.59 points. In further analysis, the score of personal burnout, work-related burnout, over-commitment and client-related burnout are 57.86, 53.83, 45.95 and 44.71. The basic attributes of nursing staff are significantly different from those of workplace fatigue with different ages, licenses, sleeping quality, self-conscious health status, number of care patients of chronic diseases and number of care people in the obstetric ward. The shift variables revealed no significant influence on workplace fatigue during the hierarchical regression analysis. About the analysis on nursing staff’s basic attributes and shift on the quality of working life, descriptive results show that the overall quality of working life of nursing staff is 3.23 points. Comparing the average score of the six aspects, the ranked average score are 3.47 (SD= .43) in interrelationship, 3.40 (SD= .46) in self-actualisation, 3.30 (SD= .40) in self-efficacy, 3.15 (SD= .38) in vocational concept, 3.07 (SD= .37) in work aspects, and 3.02 (SD= .56) in organization aspects. The basic attributes of nursing staff are significantly different from quality of working life in different marriage situations, education level, years of nursing work, occupation area, sleep quality, self-conscious health status and number of care in medical ward. There are significant differences between shift mode and shift rate with the quality of working life. The results of the hierarchical regression analysis reveal that one of the shifts variables 'shift mode' which does affect staff’s quality of working life. The workplace fatigue is negatively correlated with the quality of working life, and the over-commitment in the workplace fatigue is positively related to the vocational concept of the quality of working life. According to the regression analysis of nursing staff’s basic attributes, shift mode, workplace fatigue and quality of working life related shift, the results show that the workplace fatigue has a significant impact on nursing staff’s quality of working life. Conclusion: According to our study, shift work is correlated with workplace fatigue in nursing staffs. This results work as important reference for human resources management in hospitals to establishing a more positive and healthy work arrangement policy.

Keywords: nursing staff, shift, workplace fatigue, quality of working life

Procedia PDF Downloads 257

Authors: Saheed Shittu, Lolwa Alansari, Fahed Nattouf, Tawa Olukade, Naji Abdallah, Tamara Alshdafat, Sarra Amdouni

Abstract:

Cesarean sections (CS), a highly regarded surgical intervention for improving fetal-maternal outcomes and serving as an integral part of emergency obstetric services, are not without complications. Although CS has many advantages, it poses significant risks to both mother and child and increases healthcare expenditures in the long run. The escalating global prevalence of CS, coupled with variations in rates among immigrant populations, has prompted an inquiry into the correlation between CS rates and the nationalities of women undergoing deliveries at Al-Wakra Hospital (AWH), Qatar's second-largest public maternity hospital. This inquiry is motivated by the notable CS rate of 36%, deemed high in comparison to the 34% recorded across other Hamad Medical Corporation (HMC) maternity divisions This is Qatar's first comprehensive investigation of Caesarean section rates and nationalities. A retrospective cross-sectional study was conducted, and data for all births delivered in 2019 were retrieved from the hospital's electronic medical records. The CS rate, the crude rate, and adjusted risks of Caesarean delivery for mothers from each nationality were determined. The common indications for CS were analysed based on nationality. The association between nationality and Caesarean rates was examined using binomial logistic regression analysis considering Qatari women as a standard reference group. The correlation between the CS rate in the country of nationality and the observed CS rate in Qatar was also examined using Pearson's correlation. This study included 4,816 births from 69 different nationalities. CS was performed in 1767 women, equating to 36.5%. The nationalities with the highest CS rates were Egyptian (49.6%), Lebanese (45.5%), Filipino and Indian (both 42.2%). Qatari women recorded a CS rate of 33.4%. The major indication for elective CS was previous multiple CS (39.9%) and one prior CS, where the patient declined vaginal birth after the cesarean (VBAC) option (26.8%). A distinct pattern was noticed: elective CS was predominantly performed on Arab women, whereas emergency CS was common among women of Asian and Sub-Saharan African nationalities. Moreover, a significant correlation was found between the CS rates in Qatar and the women's countries of origin. Also, a high CS rate was linked to instances of previous CS. As a result of these insights, strategic interventions were successfully implemented at the facility to mitigate unwarranted CS, resulting in a notable reduction in CS rate from 36.5% in 2019 to 34% in 2022. This proves the efficacy of the meticulously researched approach. The focus has now shifted to reducing primary CS rates and facilitating well-informed decisions regarding childbirth methods.

Keywords: maternal nationality, caesarean section rate variation, migrants, high-income country

Procedia PDF Downloads 50

Authors: Emílie Kučerová, Tereza Veverková, Marina Morozovová, Eva Kudová, Jitka Viktorová

Abstract:

The blood-brain barrier (BBB) is a key element regulating the transport of substances between the blood and the central nervous system (CNS). The BBB protects the CNS from potentially harmful substances and maintains a suitable environment for nervous activity in the CNS, but at the same time, it represents a significant obstacle to the entry of drugs into the CNS. Pharmacoresistant epilepsy is a form of epilepsy that cannot be suppressed using two (or more) appropriately chosen antiepileptic drugs. In many cases, pharmacoresistant epilepsy is characterized by an increased concentration of efflux pumps on the luminal sides of the endothelial cells that form the BBB and an increased number of drug-metabolizing enzymes in the BBB cells, thereby preventing the effective transport of antiepileptic drugs into the CNS. Currently, a number of scientific groups are focusing on the preparation and improvement of BBB models in vitro in order to study cell interactions or transport mechanisms. However, in pathological conditions such as pharmacoresistant epilepsy, there are changes in BBB structure, and current BBB models are insufficient for related research. Our goal is to develop a suitable BBB model for pharmacoresistant epilepsy in vitro and use it to test the transfer of potential antiepileptic drugs. This model is created by co-culturing immortalized human cerebral microvascular endothelial cells, human vascular pericytes and immortalized human astrocytes. The BBB in vitro is cultivated in the form of a 2D transwell model and the integrity of the barrier is verified by measuring transendothelial electrical resistance (TEER). From the current results, a contact cell arrangement with the cultivation of endothelial cells on the upper side of the insert and the co-cultivation of astrocytes and pericytes on the lower side of the insert is selected as the most promising for BBB model cultivation. The pharmacoresistance of the BBB model is achieved by long-term cultivation of endothelial cells in an increasing concentration of selected antiepileptic drugs, which should lead to increased production of efflux pumps and drug-metabolizing enzymes. The pharmacoresistant BBB model in vitro will be further used for the screening of substances that could act both as antiepileptics and at the same time as inhibitors of efflux pumps in endothelial cells. This project was supported by the Technology Agency of the Czech Republic (TACR), Personalized Medicine: Translational research towards biomedical applications, No. TN02000109 and by the Academy of Sciences of the Czech Republic (AS CR) – grant RVO 61388963.

Keywords: antiepileptic drugs, blood-brain barrier, efflux transporters, pharmacoresistance

Procedia PDF Downloads 48