Search results for: network screening
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 5837

Search results for: network screening

1067 Enhancer: An Effective Transformer Architecture for Single Image Super Resolution

Authors: Pitigalage Chamath Chandira Peiris

Abstract:

A widely researched domain in the field of image processing in recent times has been single image super-resolution, which tries to restore a high-resolution image from a single low-resolution image. Many more single image super-resolution efforts have been completed utilizing equally traditional and deep learning methodologies, as well as a variety of other methodologies. Deep learning-based super-resolution methods, in particular, have received significant interest. As of now, the most advanced image restoration approaches are based on convolutional neural networks; nevertheless, only a few efforts have been performed using Transformers, which have demonstrated excellent performance on high-level vision tasks. The effectiveness of CNN-based algorithms in image super-resolution has been impressive. However, these methods cannot completely capture the non-local features of the data. Enhancer is a simple yet powerful Transformer-based approach for enhancing the resolution of images. A method for single image super-resolution was developed in this study, which utilized an efficient and effective transformer design. This proposed architecture makes use of a locally enhanced window transformer block to alleviate the enormous computational load associated with non-overlapping window-based self-attention. Additionally, it incorporates depth-wise convolution in the feed-forward network to enhance its ability to capture local context. This study is assessed by comparing the results obtained for popular datasets to those obtained by other techniques in the domain.

Keywords: single image super resolution, computer vision, vision transformers, image restoration

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1066 Conditionality in the European Union as a New Instrument to Guarantee the Principle of Separation of Powers

Authors: Ana Neves

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The European Union’s multi-level constitutionalism is grounded in an intricate network of vertical and horizontal legal relationships among different levels and types of public authorities. In a very significant way since the 2008 crisis, evolving institutional arrangements and institutional dynamics in the European Union have been progressively impacting Member States and the terms under which national public authorities are organised, interact and exercise their powers. This impact occurs in both macro and micro dimensions. Several examples are relevant here, such as the involvement of national Parliaments in the activities of the European Union, the enhanced integration of public administrations, the side effects of the Council framework decision on the European Arrest Warrant, the European Union Justice Scoreboard, the protection of whistle-blowers regulation, the enhanced cooperation on the establishment of the European Public Prosecutor’s Office, the regime for the protection of the Union budget and the European Rule of Law Mechanism. A common trend or denominator underlies the deepening of institutional interdependence and the increased interactions between the European Union, Member States, and public authorities at different levels. This seems to be conditionality as a general principle. The European multi-level constitutionalism must be considered in the light of this conditionality principle, which does not “imply a relationship of command and obedience”. Nevertheless, it might be more effective or be a very compelling principle. It is as if the extension of the shared rule is being accompanied by a contrapuntal dialogue. The different public authorities at various levels are being called to rethink and readjust themselves within a broader and more plural framework concerning understanding the limitation of power.

Keywords: european union -, multi-level hierarchy, conditionality, separation of powers

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1065 In and Out-Of-Sample Performance of Non Simmetric Models in International Price Differential Forecasting in a Commodity Country Framework

Authors: Nicola Rubino

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This paper presents an analysis of a group of commodity exporting countries' nominal exchange rate movements in relationship to the US dollar. Using a series of Unrestricted Self-exciting Threshold Autoregressive models (SETAR), we model and evaluate sixteen national CPI price differentials relative to the US dollar CPI. Out-of-sample forecast accuracy is evaluated through calculation of mean absolute error measures on the basis of two-hundred and fifty-three months rolling window forecasts and extended to three additional models, namely a logistic smooth transition regression (LSTAR), an additive non linear autoregressive model (AAR) and a simple linear Neural Network model (NNET). Our preliminary results confirm presence of some form of TAR non linearity in the majority of the countries analyzed, with a relatively higher goodness of fit, with respect to the linear AR(1) benchmark, in five countries out of sixteen considered. Although no model appears to statistically prevail over the other, our final out-of-sample forecast exercise shows that SETAR models tend to have quite poor relative forecasting performance, especially when compared to alternative non-linear specifications. Finally, by analyzing the implied half-lives of the > coefficients, our results confirms the presence, in the spirit of arbitrage band adjustment, of band convergence with an inner unit root behaviour in five of the sixteen countries analyzed.

Keywords: transition regression model, real exchange rate, nonlinearities, price differentials, PPP, commodity points

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1064 Neural Graph Matching for Modification Similarity Applied to Electronic Document Comparison

Authors: Po-Fang Hsu, Chiching Wei

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In this paper, we present a novel neural graph matching approach applied to document comparison. Document comparison is a common task in the legal and financial industries. In some cases, the most important differences may be the addition or omission of words, sentences, clauses, or paragraphs. However, it is a challenging task without recording or tracing the whole edited process. Under many temporal uncertainties, we explore the potentiality of our approach to proximate the accurate comparison to make sure which element blocks have a relation of edition with others. In the beginning, we apply a document layout analysis that combines traditional and modern technics to segment layouts in blocks of various types appropriately. Then we transform this issue into a problem of layout graph matching with textual awareness. Regarding graph matching, it is a long-studied problem with a broad range of applications. However, different from previous works focusing on visual images or structural layout, we also bring textual features into our model for adapting this domain. Specifically, based on the electronic document, we introduce an encoder to deal with the visual presentation decoding from PDF. Additionally, because the modifications can cause the inconsistency of document layout analysis between modified documents and the blocks can be merged and split, Sinkhorn divergence is adopted in our neural graph approach, which tries to overcome both these issues with many-to-many block matching. We demonstrate this on two categories of layouts, as follows., legal agreement and scientific articles, collected from our real-case datasets.

Keywords: document comparison, graph matching, graph neural network, modification similarity, multi-modal

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1063 Moho Undulations beneath South of Egypt, Using the Seismic Waves Generated by Tele Earthquakes

Authors: Ahmed Hosny, Haroon Elshaikh, Gaber Hassib, Yassin Ali

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The Moho discontinuity undulations beneath the southern part of Egypt have been defined using the seismic waves generated by tele earthquakes. These earthquakes have been recorded by the Aswan seismic network, which consists of 10 seismic stations established around the lake of Nasser. An additional seismic station was located towards the east of the Lake of Nasser by about ~ 150 km. Receiver functions and H-k stacking methods were used for obtaining the depths of Moho discontinuity and the Vp/Vs ratios beneath each seismic station. Our results revealed that, the depths of Moho discontinuity beneath the stations located around the Lake of Nasser range from 36 to 39 km, with an average value of 37.5 km. These results are consistent with the previous works done on the same area. The obtained Vp/Vs ratios for the crust of this area were ranged from 1.73 to 1.86, with an average value of 1.79. While beneath the station located towards the east, the Moho discontinuity was detected at a shallowest depth of 27 km and the Vp/Vs ratio was 1.82. The difference in the Moho depths beneath the stations located around the Lake of Nasser and the station located to the east revealed the boundary position between the Saharan Metacraton to the west and the Nubian-Arabian Shield to the east. This structural boundary delineates the position of the old collision of the Oceanic crust of the Nubian-Arabian Shield to the east with the Continental crust of the Saharan Metacraton to the west.

Keywords: Moho undulations, south of Egypt, seismic waves, earthquakes

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1062 Electromagnetic Interface Shielding of Graphene Oxide–Carbon Nanotube Hybrid ABS Composites

Authors: Jeevan Jyoti, Bhanu Pratap Singh, S. R. Dhakate

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In the present study, multiwalled carbon nanotubes (MWCNTs) and reduced graphene oxide (RGO) were synthesized by chemical vapor deposition and Improved Hummer’s method, respectively and their composite with acrylonitrile butadiene styrene (ABS) were prepared by twin screw co rotating extrusion technique. The electromagnetic interference (EMI) shielding effectiveness of graphene oxide carbon nanotube (GCNTs) hybrid composites was investigated and the results were compared with EMI shielding of carbon nanotube (CNTs) and reduced graphene oxide (RGO) in the frequency range of 12.4-18 GHz (Ku-band). The experimental results indicate that the EMI shielding effectiveness of these composites is achieved up to –21 dB for 10 wt. % loading of GCNT loading. The mechanism of improvement in EMI shielding effectiveness is discussed by resolving their contribution in absorption and reflection loss. The main reason for such a high improved shielding effectiveness has been attributed to the significant improvement in the electrical conductivity of the composites. The electrical conductivity of these GCNT/ABS composites was increased from 10-13 S/cm to 10-7 S/cm showing the improvement of the 6 order of the magnitude. Scanning electron microscopic (SEM) and high resolution transmission electron microscopic (HRTEM) studies showed that the GCNTs were uniformly dispersed in the ABS polymer matrix. GCNTs form a network throughout the polymer matrix and promote the reinforcement.

Keywords: ABS, EMI shielding, multiwalled carbon nanotubes, reduced graphene oxide, graphene, oxide-carbon nanotube (GCNTs), twin screw extruder, multiwall carbon nanotube, electrical conductivity

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1061 High-Resolution Spatiotemporal Retrievals of Aerosol Optical Depth from Geostationary Satellite Using Sara Algorithm

Authors: Muhammad Bilal, Zhongfeng Qiu

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Aerosols, suspended particles in the atmosphere, play an important role in the earth energy budget, climate change, degradation of atmospheric visibility, urban air quality, and human health. To fully understand aerosol effects, retrieval of aerosol optical properties such as aerosol optical depth (AOD) at high spatiotemporal resolution is required. Therefore, in the present study, hourly AOD observations at 500 m resolution were retrieved from the geostationary ocean color imager (GOCI) using the simplified aerosol retrieval algorithm (SARA) over the urban area of Beijing for the year 2016. The SARA requires top-of-the-atmosphere (TOA) reflectance, solar and sensor geometry information and surface reflectance observations to retrieve an accurate AOD. For validation of the GOCI retrieved AOD, AOD measurements were obtained from the aerosol robotic network (AERONET) version 3 level 2.0 (cloud-screened and quality assured) data. The errors and uncertainties were reported using the root mean square error (RMSE), relative percent mean error (RPME), and the expected error (EE = ± (0.05 + 0.15AOD). Results showed that the high spatiotemporal GOCI AOD observations were well correlated with the AERONET AOD measurements with a correlation coefficient (R) of 0.92, RMSE of 0.07, and RPME of 5%, and 90% of the observations were within the EE. The results suggested that the SARA is robust and has the ability to retrieve high-resolution spatiotemporal AOD observations over the urban area using the geostationary satellite.

Keywords: AEORNET, AOD, SARA, GOCI, Beijing

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1060 Statistical Analysis and Impact Forecasting of Connected and Autonomous Vehicles on the Environment: Case Study in the State of Maryland

Authors: Alireza Ansariyar, Safieh Laaly

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Over the last decades, the vehicle industry has shown increased interest in integrating autonomous, connected, and electrical technologies in vehicle design with the primary hope of improving mobility and road safety while reducing transportation’s environmental impact. Using the State of Maryland (M.D.) in the United States as a pilot study, this research investigates CAVs’ fuel consumption and air pollutants (C.O., PM, and NOx) and utilizes meaningful linear regression models to predict CAV’s environmental effects. Maryland transportation network was simulated in VISUM software, and data on a set of variables were collected through a comprehensive survey. The number of pollutants and fuel consumption were obtained for the time interval 2010 to 2021 from the macro simulation. Eventually, four linear regression models were proposed to predict the amount of C.O., NOx, PM pollutants, and fuel consumption in the future. The results highlighted that CAVs’ pollutants and fuel consumption have a significant correlation with the income, age, and race of the CAV customers. Furthermore, the reliability of four statistical models was compared with the reliability of macro simulation model outputs in the year 2030. The error of three pollutants and fuel consumption was obtained at less than 9% by statistical models in SPSS. This study is expected to assist researchers and policymakers with planning decisions to reduce CAV environmental impacts in M.D.

Keywords: connected and autonomous vehicles, statistical model, environmental effects, pollutants and fuel consumption, VISUM, linear regression models

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1059 Comparative Fragility Analysis of Shallow Tunnels Subjected to Seismic and Blast Loads

Authors: Siti Khadijah Che Osmi, Mohammed Ahmad Syed

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Underground structures are crucial components which required detailed analysis and design. Tunnels, for instance, are massively constructed as transportation infrastructures and utilities network especially in urban environments. Considering their prime importance to the economy and public safety that cannot be compromised, thus any instability to these tunnels will be highly detrimental to their performance. Recent experience suggests that tunnels become vulnerable during earthquakes and blast scenarios. However, a very limited amount of studies has been carried out to study and understanding the dynamic response and performance of underground tunnels under those unpredictable extreme hazards. In view of the importance of enhancing the resilience of these structures, the overall aims of the study are to evaluate probabilistic future performance of shallow tunnels subjected to seismic and blast loads by developing detailed fragility analysis. Critical non-linear time history numerical analyses using sophisticated finite element software Midas GTS NX have been presented about the current methods of analysis, taking into consideration of structural typology, ground motion and explosive characteristics, effect of soil conditions and other associated uncertainties on the tunnel integrity which may ultimately lead to the catastrophic failure of the structures. The proposed fragility curves for both extreme loadings are discussed and compared which provide significant information the performance of the tunnel under extreme hazards which may beneficial for future risk assessment and loss estimation.

Keywords: fragility analysis, seismic loads, shallow tunnels, blast loads

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1058 Construction Unit Rate Factor Modelling Using Neural Networks

Authors: Balimu Mwiya, Mundia Muya, Chabota Kaliba, Peter Mukalula

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Factors affecting construction unit cost vary depending on a country’s political, economic, social and technological inclinations. Factors affecting construction costs have been studied from various perspectives. Analysis of cost factors requires an appreciation of a country’s practices. Identified cost factors provide an indication of a country’s construction economic strata. The purpose of this paper is to identify the essential factors that affect unit cost estimation and their breakdown using artificial neural networks. Twenty-five (25) identified cost factors in road construction were subjected to a questionnaire survey and employing SPSS factor analysis the factors were reduced to eight. The 8 factors were analysed using the neural network (NN) to determine the proportionate breakdown of the cost factors in a given construction unit rate. NN predicted that political environment accounted 44% of the unit rate followed by contractor capacity at 22% and financial delays, project feasibility, overhead and profit each at 11%. Project location, material availability and corruption perception index had minimal impact on the unit cost from the training data provided. Quantified cost factors can be incorporated in unit cost estimation models (UCEM) to produce more accurate estimates. This can create improvements in the cost estimation of infrastructure projects and establish a benchmark standard to assist the process of alignment of work practises and training of new staff, permitting the on-going development of best practises in cost estimation to become more effective.

Keywords: construction cost factors, neural networks, roadworks, Zambian construction industry

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1057 Removal of Pharmaceuticals from Aquarius Solutions Using Hybrid Ceramic Membranes

Authors: Jenny Radeva, Anke-Gundula Roth, Christian Goebbert, Robert Niestroj-Pahl, Lars Daehne, Axel Wolfram, Juergen Wiese

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The technological advantages of ceramic filtration elements were combined with polyelectrolyte films in the development process of hybrid membrane for the elimination of pharmaceuticals from Aquarius solutions. Previously extruded alumina ceramic membranes were coated with nanosized polyelectrolyte films using Layer-by-Layer technology. The polyelectrolyte chains form a network with nano-pores on the ceramic surface and promote the retention of small molecules like pharmaceuticals and microplastics, which cannot be eliminated using standard ultrafiltration methods. Additionally, the polyelectrolyte coat contributes with its adjustable (based on application) Zeta Potential for repulsion of contaminant molecules with opposite charges. Properties like permeability, bubble point, pore size distribution and Zeta Potential of ceramic and hybrid membranes were characterized using various laboratory and pilot tests and compared with each other. The most significant role for the membrane characterization played the filtration behavior investigation, during which retention against widely used pharmaceuticals like Diclofenac, Ibuprofen and Sulfamethoxazol was subjected to series of filtration tests. The presented study offers a new perspective on nanosized molecules removal from aqueous solutions and shows the importance of combined techniques application for the elimination of pharmaceutical contaminants from drinking water.

Keywords: water treatment, hybrid membranes, layer-by-layer coating, filtration, polyelectrolytes

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1056 Identifying Enablers and Barriers of Healthcare Knowledge Transfer: A Systematic Review

Authors: Yousuf Nasser Al Khamisi

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Purpose: This paper presents a Knowledge Transfer (KT) Framework in healthcare sectors by applying a systematic literature review process to the healthcare organizations domain to identify enablers and barriers of KT in Healthcare. Methods: The paper conducted a systematic literature search of peer-reviewed papers that described key elements of KT using four databases (Medline, Cinahl, Scopus, and Proquest) for a 10-year period (1/1/2008–16/10/2017). The results of the literature review were used to build a conceptual framework of KT in healthcare organizations. The author used a systematic review of the literature, as described by Barbara Kitchenham in Procedures for Performing Systematic Reviews. Findings: The paper highlighted the impacts of using Knowledge Management (KM) concept at a healthcare organization in controlling infectious diseases in hospitals, improving family medicine performance and enhancing quality improvement practices. Moreover, it found that good-coding performance is analytically linked with a knowledge sharing network structure rich in brokerage and hierarchy rather than in density. The unavailability or ignored of the latest evidence on more cost-effective or more efficient delivery approaches leads to increase the healthcare costs and may lead to unintended results. Originality: Search procedure produced 12,093 results, of which 3523 were general articles about KM and KT. The titles and abstracts of these articles had been screened to segregate what is related and what is not. 94 articles identified by the researchers for full-text assessment. The total number of eligible articles after removing un-related articles was 22 articles.

Keywords: healthcare organisation, knowledge management, knowledge transfer, KT framework

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1055 Using Technology to Deliver and Scale Early Childhood Development Services in Resource Constrained Environments: Case Studies from South Africa

Authors: Sonja Giese, Tess N. Peacock

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South African based Innovation Edge is experimenting with technology to drive positive behavior change, enable data-driven decision making, and scale quality early years services. This paper uses five case studies to illustrate how technology can be used in resource-constrained environments to first, encourage parenting practices that build early language development (using a stage-based mobile messaging pilot, ChildConnect), secondly, to improve the quality of ECD programs (using a mobile application, CareUp), thirdly, how to affordably scale services for the early detection of visual and hearing impairments (using a mobile tool, HearX), fourthly, how to build a transparent and accountable system for the registration and funding of ECD (using a blockchain enabled platform, Amply), and finally enable rapid data collection and feedback to facilitate quality enhancement of programs at scale (the Early Learning Outcomes Measure). ChildConnect and CareUp were both developed using a design based iterative research approach. The usage and uptake of ChildConnect and CareUp was evaluated with qualitative and quantitative methods. Actual child outcomes were not measured in the initial pilots. Although parents who used and engaged on either platform felt more supported and informed, parent engagement and usage remains a challenge. This is contrast to ECD practitioners whose usage and knowledge with CareUp showed both sustained engagement and knowledge improvement. HearX is an easy-to-use tool to identify hearing loss and visual impairment. The tool was tested with 10000 children in an informal settlement. The feasibility of cost-effectively decentralising screening services was demonstrated. Practical and financial barriers remain with respect to parental consent and for successful referrals. Amply uses mobile and blockchain technology to increase impact and accountability of public services. In the pilot project, Amply is being used to replace an existing paper-based system to register children for a government-funded pre-school subsidy in South Africa. Early Learning Outcomes Measure defines what it means for a child to be developmentally ‘on track’ at aged 50-69 months. ELOM administration is enabled via a tablet which allows for easy and accurate data collection, transfer, analysis, and feedback. ELOM is being used extensively to drive quality enhancement of ECD programs across multiple modalities. The nature of ECD services in South Africa is that they are in large part provided by disconnected private individuals or Non-Governmental Organizations (in contrast to basic education which is publicly provided by the government). It is a disparate sector which means that scaling successful interventions is that much harder. All five interventions show the potential of technology to support and enhance a range of ECD services, but pathways to scale are still being tested.

Keywords: assessment, behavior change, communication, data, disabilities, mobile, scale, technology, quality

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1054 Determining of the Performance of Data Mining Algorithm Determining the Influential Factors and Prediction of Ischemic Stroke: A Comparative Study in the Southeast of Iran

Authors: Y. Mehdipour, S. Ebrahimi, A. Jahanpour, F. Seyedzaei, B. Sabayan, A. Karimi, H. Amirifard

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Ischemic stroke is one of the common reasons for disability and mortality. The fourth leading cause of death in the world and the third in some other sources. Only 1/3 of the patients with ischemic stroke fully recover, 1/3 of them end in permanent disability and 1/3 face death. Thus, the use of predictive models to predict stroke has a vital role in reducing the complications and costs related to this disease. Thus, the aim of this study was to specify the effective factors and predict ischemic stroke with the help of DM methods. The present study was a descriptive-analytic study. The population was 213 cases from among patients referring to Ali ibn Abi Talib (AS) Hospital in Zahedan. Data collection tool was a checklist with the validity and reliability confirmed. This study used DM algorithms of decision tree for modeling. Data analysis was performed using SPSS-19 and SPSS Modeler 14.2. The results of the comparison of algorithms showed that CHAID algorithm with 95.7% accuracy has the best performance. Moreover, based on the model created, factors such as anemia, diabetes mellitus, hyperlipidemia, transient ischemic attacks, coronary artery disease, and atherosclerosis are the most effective factors in stroke. Decision tree algorithms, especially CHAID algorithm, have acceptable precision and predictive ability to determine the factors affecting ischemic stroke. Thus, by creating predictive models through this algorithm, will play a significant role in decreasing the mortality and disability caused by ischemic stroke.

Keywords: data mining, ischemic stroke, decision tree, Bayesian network

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1053 A Historical Overview and Supplementation of the Dyad Concept of Industrial Marketing

Authors: Kimmo J. Kurppa

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This paper describes the development of the buyer-supplier dyad concept over the years and proposes improvements, clarifications and extensions to the prevailing definitions published in 1970’s and 1980’s. This paper suggests a partition of the buyer-supplier dyad to concepts of Commercial Dyad (dyadic interaction in vertical relationships) and Innovative Dyad (dyadic interaction in horizontal relationship) since dyadic interaction takes place in two major types of contexts between industrial firms. Especially the context of joint product development in a dyadic relationship has not been adequately recognized being totally different from the interaction taking place in commercial buyer-supplier interaction. This paper provides therefore a solution to the existing gap in research by clarifying the descriptions and the context where dyadic interaction takes place between industrial firms. This paper also illustrates and explains how the firm’s organization and the interaction taking place inside it, is connected to the dyadic interaction structure between the firm and its partner firm. This theme has been discussed earlier but the phenomenon has not been adequately described and has not been illustrated in earlier research. This conceptual study has been interested in how the dyad concept of Industrial Marketing has been defined in the earlier research and how the definition could be improved. This conceptual paper has been constructed by using the systematic review methodology and proposes avenues for future research. The concept and existence of relationship and interaction between firm’s internal interaction network and external interaction between firm’s dyadic counterparts, need to be verified through empirical research.

Keywords: dyadic interaction, industrial dyad, buyer-supplier relationship, strategic reciprocity, experience, socially adjusted opportunism

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1052 Photocatalysis with Fe/Ti-Pillared Clays for the Oxofunctionalization of Alkylaromatics by O2

Authors: Houria Rezala, Jose Luis Valverde, Amaya Romero, Alessandra Molinari, Andrea Maldotti

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A pillared montmorillonite containing iron doped titania (Fe/Ti-PILC) has been prepared from a natural clay. This material has been characterized by X-ray diffraction, nitrogen adsorption, temperature programmed desorption of ammonia, inductively coupled plasma atomic emission spectroscopy, atomic absorption, and diffuse reflectance UV-VIS spectroscopy. The layer structure of Fe/Ti-PILC resulted to be ordered with an insertion of pillars, which caused a slight increase in the basal spacing of the clay. Its specific surface area was about three times larger than that of the parent Na-montmorillonite due principally to the creation of a remarkable microporous network. The doped material was a robust photocatalyst able to oxidize liquid alkyl aromatics to the corresponding carbonylic derivatives, using O2 as the oxidizing species, at mild pressure and temperature conditions. Accumulation of valuable carbonylic derivatives was possible since their over-oxidation to carbon dioxide was negligible. Fe/Ti-PILC was able to discriminate between toluene and cyclohexane in favor of the aromatic compound with an efficiency that is about three times higher than that of titanium pillared clays (Ti-PILC). It is likely that the addition of iron favored the formation of new acid sites able to interact with the aromatic substrate. Iron doping caused a significant TiO2 visible light-induced activity (wavelength > 400 nm) with only minor negative effects on its performance under UV-light irradiation (wavelength > 290 nm).

Keywords: alkyl aromatics oxidation, heterogeneous photocatalysis, iron doping, pillared clays

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1051 Sexting Phenomenon in Educational Settings: A Data Mining Approach

Authors: Koutsopoulou Ioanna, Gkintoni Evgenia, Halkiopoulos Constantinos, Antonopoulou Hera

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Recent advances in Internet Computer Technology (ICT) and the ever-increasing use of technological equipment amongst adolescents and young adults along with unattended access to the internet and social media and uncontrolled use of smart phones and PCs have caused social problems like sexting to emerge. The main purpose of the present article is first to present an analytic theoretical framework of sexting as a recent social phenomenon based on studies that have been conducted the last decade or so; and second to investigate Greek students’ and also social network users, sexting perceptions and to record how often social media users exchange sexual messages and to retrace demographic variables predictors. Data from 1,000 students were collected and analyzed and all statistical analysis was done by the software package WEKA. The results indicate among others, that the use of data mining methods is an important tool to draw conclusions that could affect decision and policy making especially in the field and related social topics of educational psychology. To sum up, sexting lurks many risks for adolescents and young adults students in Greece and needs to be better addressed in relevance to the stakeholders as well as society in general. Furthermore, policy makers, legislation makers and authorities will have to take action to protect minors. Prevention strategies based on Greek cultural specificities are being proposed. This social problem has raised concerns in recent years and will most likely escalate concerns in global communities in the future.

Keywords: educational ethics, sexting, Greek sexters, sex education, data mining

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1050 Impact of Primary Care Telemedicine Consultations On Health Care Resource Utilisation: A Systematic Review

Authors: Anastasia Constantinou, Stephen Morris

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Background: The adoption of synchronous and asynchronous telemedicine modalities for primary care consultations has exponentially increased since the COVID-19 pandemic. However, there is limited understanding of how virtual consultations influence healthcare resource utilization and other quality measures including safety, timeliness, efficiency, patient and provider satisfaction, cost-effectiveness and environmental impact. Aim: Quantify the rate of follow-up visits, emergency department visits, hospitalizations, request for investigations and prescriptions and comment on the effect on different quality measures associated with different telemedicine modalities used for primary care services and primary care referrals to secondary care Design and setting: Systematic review in primary care Methods: A systematic search was carried out across three databases (Medline, PubMed and Scopus) between August and November 2023, using terms related to telemedicine, general practice, electronic referrals, follow-up, use and efficiency and supported by citation searching. This was followed by screening according to pre-defined criteria, data extraction and critical appraisal. Narrative synthesis and metanalysis of quantitative data was used to summarize findings. Results: The search identified 2230 studies; 50 studies are included in this review. There was a prevalence of asynchronous modalities in both primary care services (68%) and referrals from primary care to secondary care (83%), and most of the study participants were females (63.3%), with mean age of 48.2. The average follow-up for virtual consultations in primary care was 28.4% (eVisits: 36.8%, secure messages 18.7%, videoconference 23.5%) with no significant difference between them or F2F consultations. There was an average annual reduction of primary care visits by 0.09/patient, an increase in telephone visits by 0.20/patient, an increase in ED encounters by 0.011/patient, an increase in hospitalizations by 0.02/patient and an increase in out of hours visits by 0.019/patient. Laboratory testing was requested on average for 10.9% of telemedicine patients, imaging or procedures for 5.6% and prescriptions for 58.7% of patients. When looking at referrals to secondary care, on average 36.7% of virtual referrals required follow-up visit, with the average rate of follow-up for electronic referrals being higher than for videoconferencing (39.2% vs 23%, p=0.167). Technical failures were reported on average for 1.4% of virtual consultations to primary care. When using carbon footprint estimates, we calculate that the use of telemedicine in primary care services can potentially provide a net decrease in carbon footprint by 0.592kgCO2/patient/year. When follow-up rates are taken into account, we estimate that virtual consultations reduce carbon footprint for primary care services by 2.3 times, and for secondary care referrals by 2.2 times. No major concerns regarding quality of care, or patient satisfaction were identified. 5/7 studies that addressed cost-effectiveness, reported increased savings. Conclusions: Telemedicine provides quality, cost-effective, and environmentally sustainable care for patients in primary care with inconclusive evidence regarding the rates of subsequent healthcare utilization. The evidence is limited by heterogeneous, small-scale studies and lack of prospective comparative studies. Further research to identify the most appropriate telemedicine modality for different patient populations, clinical presentations, service provision (e.g. used to follow-up patients instead of initial diagnosis) as well as further education for patients and providers alike on how to make best use of this service is expected to improve outcomes and influence practice.

Keywords: telemedicine, healthcare utilisation, digital interventions, environmental impact, sustainable healthcare

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1049 The Effect Human Papilloma Virus on Pregnancy Outcome

Authors: Amrit Gupta, Suchi Rani, Vineeta Agarwal, Swast Tiwari, Anup Kumar, Sachin Sharma

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Pregnancy is a unique state in which a balance of immune tolerance and suppression is necessary to protect the fetus without compromising the mother’s health. Human papilloma virus (HPV) is viral infection which mainly gets transmitted through sexual contact. The HPV infection can cause infections in the placenta and increase the inflammatory response in the mother, affecting pregnancy outcomes. This may result in adverse maternal and neonatal outcomes. The objectives of this research are to evaluate the effect on clinical course in pregnancy and maternal outcome in pregnant women with HPV infection and to evaluate the effect on neonatal health in terms of adverse clinical effects. Methodology: The prospective cohort study was done in a tertiary care institution over two years. In this study, 250 participants were recruited. The study included pregnant women who attended the antenatal clinic for routine check-ups. Written informed consent was obtained from each participant. Participants were asked to fill out a detailed questionnaire about their lifestyle, including demographic characteristics, sexual behaviors, past gynecological history, and medical and surgical history. HPV was the preliminary screening method, and a Pap smear was done in patients who came out to be HPV positive. Samples were collected with the cotton stick or HC2 sampler brush. Cyto-brush was rotated 3–5 times in the region of ecto-cervix. After the collection of the sample, it was dissolved in PBS buffer and stored at − 80° for HPV DNA analysis. HPV DNA was detected using a hybrid capture assay (marketed as Digene HC2 high-risk HPV DNA test; Cat. No./ID: 5199–1220). The cohort was divided into two study groups: 1) those who were HPV positive and 2) those who were HPV negative. The chi-square test is used to compare categorical variables across groups. AQ5 Unpaired t-tests and independent sample tests are used to test the statistical significance of intergroup mean differences. P-values are considered significant if they are less than 0.05. In MS Windows, SPSS20 (IBM Corporation; NY, USA) was used for statistical analysis of all data. Results: Out of 228 pregnant women, 27.63% (n=63) of pregnant women were found positive for the HPV DNA test. In comparing the HPV-positive (N=63) and HPV-negative (N=165) groups using chi-square tests, several demographic variables exhibited statistically significant differences. Habitat distribution shows a significant difference (p<0.001), with 28.6% of HPV-positive individuals residing in rural areas compared to 8.5% of HPV-negative individuals. The presence of morbidity besides HPV infection differed significantly (p<0.001), with HPV-positive participants more likely to have additional morbidities (54%) compared to HPV-negative participants (32.1%). The mode of delivery showed significant differences (p<0.05), particularly in emergency lower segment cesarean section (HPV+: 41.3%, HPV-: 23.6%). Gestational age at delivery was significantly lower in the HPV-positive group (median 37.28 weeks, IQR 36.43-37.85) compared to the HPV-negative group (median 37.71 weeks, IQR 37.14-38.42), with a P-value of 0.003. Finally, birth weight was significantly lower in the HPV-positive group (median 2.75 kg, IQR 2.5-2.9425) compared to the HPV-negative group (median 2.9 kg, IQR 2.67-3.25) with a P-value of 0.001. Conclusion: In summary, our study offers valuable insights into the relationship between HPV infection during pregnancy, basic demographic factors and maternal and neonatal health outcomes.

Keywords: human papilloma virus, maternal health, fetal outcome, pregnancy

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1048 Selective Oxidation of 6Mn-2Si Advanced High Strength Steels during Intercritical Annealing Treatment

Authors: Maedeh Pourmajidian, Joseph R. McDermid

Abstract:

Advanced High Strength Steels are revolutionizing both the steel and automotive industries due to their high specific strength and ability to absorb energy during crash events. This allows manufacturers to design vehicles with significantly increased fuel efficiency without compromising passenger safety. To maintain the structural integrity of the fabricated parts, they must be protected from corrosion damage through continuous hot-dip galvanizing process, which is challenging due to selective oxidation of Mn and Si on the surface of this AHSSs. The effects of process atmosphere oxygen partial pressure and small additions of Sn on the selective oxidation of a medium-Mn C-6Mn-2Si advanced high strength steel was investigated. Intercritical annealing heat treatments were carried out at 690˚C in an N2-5%H2 process atmosphere under dew points ranging from –50˚C to +5˚C. Surface oxide chemistries, morphologies, and thicknesses were determined at a variety of length scales by several techniques, including SEM, TEM+EELS, and XPS. TEM observations of the sample cross-sections revealed the transition to internal oxidation at the +5˚C dew point. EELS results suggested that the internal oxides network was composed of a multi-layer oxide structure with varying chemistry from oxide core towards the outer part. The combined effect of employing a known surface active element as a function of process atmosphere on the surface structure development and the possible impact on reactive wetting of the steel substrates by the continuous galvanizing zinc bath will be discussed.

Keywords: 3G AHSS, hot-dip galvanizing, oxygen partial pressure, selective oxidation

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1047 Springback Prediction for Sheet Metal Cold Stamping Using Convolutional Neural Networks

Authors: Lei Zhu, Nan Li

Abstract:

Cold stamping has been widely applied in the automotive industry for the mass production of a great range of automotive panels. Predicting the springback to ensure the dimensional accuracy of the cold-stamped components is a critical step. The main approaches for the prediction and compensation of springback in cold stamping include running Finite Element (FE) simulations and conducting experiments, which require forming process expertise and can be time-consuming and expensive for the design of cold stamping tools. Machine learning technologies have been proven and successfully applied in learning complex system behaviours using presentative samples. These technologies exhibit the promising potential to be used as supporting design tools for metal forming technologies. This study, for the first time, presents a novel application of a Convolutional Neural Network (CNN) based surrogate model to predict the springback fields for variable U-shape cold bending geometries. A dataset is created based on the U-shape cold bending geometries and the corresponding FE simulations results. The dataset is then applied to train the CNN surrogate model. The result shows that the surrogate model can achieve near indistinguishable full-field predictions in real-time when compared with the FE simulation results. The application of CNN in efficient springback prediction can be adopted in industrial settings to aid both conceptual and final component designs for designers without having manufacturing knowledge.

Keywords: springback, cold stamping, convolutional neural networks, machine learning

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1046 Factors Affecting Treatment Resilience in Patients with Oesophago-Gastric Cancers Undergoing Palliative Chemotherapy: A Literature Review

Authors: Kiran Datta, Daniella Holland-Hart, Anthony Byrne

Abstract:

Introduction: Oesophago-gastric (OG) cancers are the fifth commonest in the UK, accounting for over 12,000 deaths each year. Most patients will present at later stages of the disease, with only 21% of patients with stage 4 disease surviving longer than a year. As a result, many patients are unsuitable for curative surgery and instead receive palliative treatment to improve prognosis and symptom burden. However, palliative chemotherapy can result in significant toxicity: almost half of the patients are unable to complete their chemotherapy regimen, with this proportion rising significantly in older and frailer patients. In addition, clinical trials often exclude older and frailer patients due to strict inclusion criteria, meaning there is limited evidence to guide which patients are most likely to benefit from palliative chemotherapy. Inappropriate chemotherapy administration is at odds with the goals of palliative treatment and care, which are to improve quality of life, and this also represents a significant resource expenditure. This literature review aimed to examine and appraise evidence regarding treatment resilience in order to guide clinicians in identifying the most suitable candidates for palliative chemotherapy. Factors influencing treatment resilience were assessed, as measured by completion rates, dose reductions, and toxicities. Methods: This literature review was conducted using rapid review methodology, utilising modified systematic methods. A literature search was performed across the MEDLINE, EMBASE, and Cochrane Library databases, with results limited to papers within the last 15 years and available in English. Key inclusion criteria included: 1) participants with either oesophageal, gastro-oesophageal junction, or gastric cancers; 2) patients treated with palliative chemotherapy; 3) available data evaluating the association between baseline participant characteristics and treatment resilience. Results: Of the 2326 papers returned, 11 reports of 10 studies were included in this review after excluding duplicates and irrelevant papers. Treatment resilience factors that were assessed included: age, performance status, frailty, inflammatory markers, and sarcopenia. Age was generally a poor predictor for how well patients would tolerate chemotherapy, while poor performance status was a better indicator of the need for dose reduction and treatment non-completion. Frailty was assessed across one cohort using multiple screening tools and was an effective marker of the risk of toxicity and the requirement for dose reduction. Inflammatory markers included lymphopenia and the Glasgow Prognostic Score, which assessed inflammation and hypoalbuminaemia. Although quick to obtain and interpret, these findings appeared less reliable due to the inclusion of patients treated with palliative radiotherapy. Sarcopenia and body composition were often associated with chemotherapy toxicity but not the rate of regimen completion. Conclusion: This review demonstrates that there are numerous measures that can estimate the ability of patients with oesophago-gastric cancer to tolerate palliative chemotherapy, and these should be incorporated into clinical assessments to promote personalised decision-making around treatment. Age should not be a barrier to receiving chemotherapy and older and frailer patients should be included in future clinical trials to better represent typical patients with oesophago-gastric cancers. Decisions regarding palliative treatment should be guided by these factors identified as well as patient preference.

Keywords: frailty, oesophago-gastric cancer, palliative chemotherapy, treatment resilience

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1045 Automated Distribution System Management: Substation Remote Diagnostic and Operation Solution for Obafemi Awolowo University

Authors: Aderonke Oluseun Akinwumi, Olusola A. Komolaf

Abstract:

This paper gives information about the wide array of challenges facing both the electric utilities and consumers in the distribution system in developing countries, using Obafemi Awolowo University, Ile-Ife Nigeria as a case study. It also proffers cost-effective solution through remote monitoring, diagnostic and operation of distribution networks without compromising the system reliability. As utilities move from manned and unintelligent networks to completely unmanned smart grids, switching activities at substations and feeders will be managed and controlled remotely by dedicated systems hence this design. The Substation Remote Diagnostic and Operation Solution (sRDOs) would remotely monitor the load on Medium Voltage (MV) and Low Voltage (LV) feeders as well as distribution transformers and allow the utility disconnect non-paying customers with absolutely no extra resource deployment and without interrupting supply to paying customers. The aftermath of the implementation of this design improved the lifetime of key distribution infrastructure by automatically isolating feeders during overload conditions and more importantly erring consumers. This increased the ratio of revenue generated on electricity bills to total network load.

Keywords: electric utility, consumers, remote monitoring, diagnostic, system reliability, manned and unintelligent networks, unmanned smart grids, switching activities, medium voltage, low voltage, distribution transformer

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1044 Estimation of Twist Loss in the Weft Yarn during Air-Jet Weft Insertion

Authors: Muhammad Umair, Yasir Nawab, Khubab Shaker, Muhammad Maqsood, Adeel Zulfiqar, Danish Mahmood Baitab

Abstract:

Fabric is a flexible woven material consisting of a network of natural or artificial fibers often referred to as thread or yarn. Today fabrics are produced by weaving, braiding, knitting, tufting and non-woven. Weaving is a method of fabric production in which warp and weft yarns are interlaced perpendicular to each other. There is infinite number of ways for the interlacing of warp and weft yarn. Each way produces a different fabric structure. The yarns parallel to the machine direction are called warp yarns and the yarns perpendicular to the machine direction are called weft or filling yarns. Air jet weaving is the modern method of weft insertion and considered as high speed loom. The twist loss in air jet during weft insertion affects the strength. The aim of this study was to investigate the effect of twist change in weft yarn during air-jet weft insertion. A total number of 8 samples were produced using 1/1 plain and 3/1 twill weave design with two fabric widths having same loom settings. Two different types of yarns like cotton and PC blend were used. The effect of material type, weave design and fabric width on twist change of weft yarn was measured and discussed. Twist change in the different types of weft yarn and weave design was measured and compared the twist change in the weft yarn with the yarn before weft yarn insertion and twist loss is measured. Wider fabric leads to higher twist loss in the yarn.

Keywords: air jet loom, twist per inch, twist loss, weft yarn

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1043 Neuroinflammation in Late-Life Depression: The Role of Glial Cells

Authors: Chaomeng Liu, Li Li, Xiao Wang, Li Ren, Qinge Zhang

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Late-life depression (LLD) is a prevalent mental disorder among the elderly, frequently accompanied by significant cognitive decline, and has emerged as a worldwide public health concern. Microglia, astrocytes, and peripheral immune cells play pivotal roles in regulating inflammatory responses within the central nervous system (CNS) across diverse cerebral disorders. This review commences with the clinical research findings and accentuates the recent advancements pertaining to microglia and astrocytes in the neuroinflammation process of LLD. The reciprocal communication network between the CNS and immune system is of paramount importance in the pathogenesis of depression and cognitive decline. Stress-induced downregulation of tight and gap junction proteins in the brain results in increased blood-brain barrier permeability and impaired astrocyte function. Concurrently, activated microglia release inflammatory mediators, initiating the kynurenine metabolic pathway and exacerbating the quinolinic acid/kynurenic acid imbalance. Moreover, the balance between Th17 and Treg cells is implicated in the preservation of immune homeostasis within the cerebral milieu of individuals suffering from LLD. The ultimate objective of this review is to present future strategies for the management and treatment of LLD, informed by the most recent advancements in research, with the aim of averting or postponing the onset of AD.

Keywords: neuroinflammation, late-life depression, microglia, astrocytes, central nervous system, blood-brain barrier, Kynurenine pathway

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1042 Downscaling Seasonal Sea Surface Temperature Forecasts over the Mediterranean Sea Using Deep Learning

Authors: Redouane Larbi Boufeniza, Jing-Jia Luo

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This study assesses the suitability of deep learning (DL) for downscaling sea surface temperature (SST) over the Mediterranean Sea in the context of seasonal forecasting. We design a set of experiments that compare different DL configurations and deploy the best-performing architecture to downscale one-month lead forecasts of June–September (JJAS) SST from the Nanjing University of Information Science and Technology Climate Forecast System version 1.0 (NUIST-CFS1.0) for the period of 1982–2020. We have also introduced predictors over a larger area to include information about the main large-scale circulations that drive SST over the Mediterranean Sea region, which improves the downscaling results. Finally, we validate the raw model and downscaled forecasts in terms of both deterministic and probabilistic verification metrics, as well as their ability to reproduce the observed precipitation extreme and spell indicator indices. The results showed that the convolutional neural network (CNN)-based downscaling consistently improves the raw model forecasts, with lower bias and more accurate representations of the observed mean and extreme SST spatial patterns. Besides, the CNN-based downscaling yields a much more accurate forecast of extreme SST and spell indicators and reduces the significant relevant biases exhibited by the raw model predictions. Moreover, our results show that the CNN-based downscaling yields better skill scores than the raw model forecasts over most portions of the Mediterranean Sea. The results demonstrate the potential usefulness of CNN in downscaling seasonal SST predictions over the Mediterranean Sea, particularly in providing improved forecast products.

Keywords: Mediterranean Sea, sea surface temperature, seasonal forecasting, downscaling, deep learning

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1041 Physiological Effects during Aerobatic Flights on Science Astronaut Candidates

Authors: Pedro Llanos, Diego García

Abstract:

Spaceflight is considered the last frontier in terms of science, technology, and engineering. But it is also the next frontier in terms of human physiology and performance. After more than 200,000 years humans have evolved under earth’s gravity and atmospheric conditions, spaceflight poses environmental stresses for which human physiology is not adapted. Hypoxia, accelerations, and radiation are among such stressors, our research involves suborbital flights aiming to develop effective countermeasures in order to assure sustainable human space presence. The physiologic baseline of spaceflight participants is subject to great variability driven by age, gender, fitness, and metabolic reserve. The objective of the present study is to characterize different physiologic variables in a population of STEM practitioners during an aerobatic flight. Cardiovascular and pulmonary responses were determined in Science Astronaut Candidates (SACs) during unusual attitude aerobatic flight indoctrination. Physiologic data recordings from 20 subjects participating in high-G flight training were analyzed. These recordings were registered by wearable sensor-vest that monitored electrocardiographic tracings (ECGs), signs of dysrhythmias or other electric disturbances during all the flight. The same cardiovascular parameters were also collected approximately 10 min pre-flight, during each high-G/unusual attitude maneuver and 10 min after the flights. The ratio (pre-flight/in-flight/post-flight) of the cardiovascular responses was calculated for comparison of inter-individual differences. The resulting tracings depicting the cardiovascular responses of the subjects were compared against the G-loads (Gs) during the aerobatic flights to analyze cardiovascular variability aspects and fluid/pressure shifts due to the high Gs. In-flight ECG revealed cardiac variability patterns associated with rapid Gs onset in terms of reduced heart rate (HR) and some scattered dysrhythmic patterns (15% premature ventricular contractions-type) that were considered as triggered physiological responses to high-G/unusual attitude training and some were considered as instrument artifact. Variation events were observed in subjects during the +Gz and –Gz maneuvers and these may be due to preload and afterload, sudden shift. Our data reveal that aerobatic flight influenced the breathing rate of the subject, due in part by the various levels of energy expenditure due to the increased use of muscle work during these aerobatic maneuvers. Noteworthy was the high heterogeneity in the different physiological responses among a relatively small group of SACs exposed to similar aerobatic flights with similar Gs exposures. The cardiovascular responses clearly demonstrated that SACs were subjected to significant flight stress. Routine ECG monitoring during high-G/unusual attitude flight training is recommended to capture pathology underlying dangerous dysrhythmias in suborbital flight safety. More research is currently being conducted to further facilitate the development of robust medical screening, medical risk assessment approaches, and suborbital flight training in the context of the evolving commercial human suborbital spaceflight industry. A more mature and integrative medical assessment method is required to understand the physiology state and response variability among highly diverse populations of prospective suborbital flight participants.

Keywords: g force, aerobatic maneuvers, suborbital flight, hypoxia, commercial astronauts

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1040 Implementation of Conceptual Real-Time Embedded Functional Design via Drive-By-Wire ECU Development

Authors: Ananchai Ukaew, Choopong Chauypen

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Design concepts of real-time embedded system can be realized initially by introducing novel design approaches. In this literature, model based design approach and in-the-loop testing were employed early in the conceptual and preliminary phase to formulate design requirements and perform quick real-time verification. The design and analysis methodology includes simulation analysis, model based testing, and in-the-loop testing. The design of conceptual drive-by-wire, or DBW, algorithm for electronic control unit, or ECU, was presented to demonstrate the conceptual design process, analysis, and functionality evaluation. The concepts of DBW ECU function can be implemented in the vehicle system to improve electric vehicle, or EV, conversion drivability. However, within a new development process, conceptual ECU functions and parameters are needed to be evaluated. As a result, the testing system was employed to support conceptual DBW ECU functions evaluation. For the current setup, the system components were consisted of actual DBW ECU hardware, electric vehicle models, and control area network or CAN protocol. The vehicle models and CAN bus interface were both implemented as real-time applications where ECU and CAN protocol functionality were verified according to the design requirements. The proposed system could potentially benefit in performing rapid real-time analysis of design parameters for conceptual system or software algorithm development.

Keywords: drive-by-wire ECU, in-the-loop testing, model-based design, real-time embedded system

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1039 In-Farm Wood Gasification Energy Micro-Generation System in Brazil: A Monte Carlo Viability Simulation

Authors: Erich Gomes Schaitza, Antônio Francisco Savi, Glaucia Aparecida Prates

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The penetration of renewable energy into the electricity supply in Brazil is high, one of the highest in the World. Centralized hydroelectric generation is the main source of energy, followed by biomass and wind. Surprisingly, mini and micro-generation are negligible, with less than 2,000 connections to the national grid. In 2015, a new regulatory framework was put in place to change this situation. In the agricultural sector, the framework was complemented by the offer of low interest rate loans to in-farm renewable generation. Brazil proposed to more than double its area of planted forests as part of its INDC- Intended Nationally Determined Contributions to the UNFCCC-U.N. Framework Convention on Climate Change (UNFCCC). This is an ambitious target which will be achieved only if forests are attractive to farmers. Therefore, this paper analyses whether planting forests for in-farm energy generation with a with a woodchip gasifier is economically viable for microgeneration under the new framework and at if they could be an economic driver for forest plantation. At first, a static case was analyzed with data from Eucalyptus plantations in five farms. Then, a broader analysis developed with the use of Monte Carlo technique. Planting short rotation forests to generate energy could be a viable alternative and the low interest loans contribute to that. There are some barriers to such systems such as the inexistence of a mature market for small scale equipment and of a reference network of good practices and examples.

Keywords: biomass, distribuited generation, small-scale, Monte Carlo

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1038 Broad Host Range Bacteriophage Cocktail for Reduction of Staphylococcus aureus as Potential Therapy for Atopic Dermatitis

Authors: Tamar Lin, Nufar Buchshtab, Yifat Elharar, Julian Nicenboim, Rotem Edgar, Iddo Weiner, Lior Zelcbuch, Ariel Cohen, Sharon Kredo-Russo, Inbar Gahali-Sass, Naomi Zak, Sailaja Puttagunta, Merav Bassan

Abstract:

Background: Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disorder that is characterized by dry skin and flares of eczematous lesions and intense pruritus. Multiple lines of evidence suggest that AD is associated with increased colonization by Staphylococcus aureus, which contributes to disease pathogenesis through the release of virulence factors that affect both keratinocytes and immune cells, leading to disruption of the skin barrier and immune cell dysfunction. The aim of the current study is to develop a bacteriophage-based product that specifically targets S. aureus. Methods: For the discovery of phage, environmental samples were screened on 118 S. aureus strains isolated from skin samples, followed by multiple enrichment steps. Natural phages were isolated, subjected to Next-generation Sequencing (NGS), and analyzed using proprietary bioinformatics tools for undesirable genes (toxins, antibiotic resistance genes, lysogeny potential), taxonomic classification, and purity. Phage host range was determined by an efficiency of plating (EOP) value above 0.1 and the ability of the cocktail to completely lyse liquid bacterial culture under different growth conditions (e.g., temperature, bacterial stage). Results: Sequencing analysis demonstrated that the 118 S. aureus clinical strains were distributed across the phylogenetic tree of all available Refseq S. aureus (~10,750 strains). Screening environmental samples on the S. aureus isolates resulted in the isolation of 50 lytic phages from different genera, including Silviavirus, Kayvirus, Podoviridae, and a novel unidentified phage. NGS sequencing confirmed the absence of toxic elements in the phages’ genomes. The host range of the individual phages, as measured by the efficiency of plating (EOP), ranged between 41% (48/118) to 79% (93/118). Host range studies in liquid culture revealed that a subset of the phages can infect a broad range of S. aureus strains in different metabolic states, including stationary state. Combining the single-phage EOP results of selected phages resulted in a broad host range cocktail which infected 92% (109/118) of the strains. When tested in vitro in a liquid infection assay, clearance was achieved in 87% (103/118) of the strains, with no evidence of phage resistance throughout the study (24 hours). A S. aureus host was identified that can be used for the production of all the phages in the cocktail at high titers suitable for large-scale manufacturing. This host was validated for the absence of contaminating prophages using advanced NGS methods combined with multiple production cycles. The phages are produced under optimized scale-up conditions and are being used for the development of a topical formulation (BX005) that may be administered to subjects with atopic dermatitis. Conclusions: A cocktail of natural phages targeting S. aureus was effective in reducing bacterial burden across multiple assays. Phage products may offer safe and effective steroid-sparing options for atopic dermatitis.

Keywords: atopic dermatitis, bacteriophage cocktail, host range, Staphylococcus aureus

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