Search results for: forming limit curve (FLC)

Authors: Mishell E. Cabrera, Bryan G. Valencia, Anderson I. Guamán

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Human dependence on plastic products has led to global pollution, with plastic particles ranging in size from 0.001 to 5 millimeters, which are called microplastics (hereafter, MPs). The abundance of microplastics is used as an indicator of pollution. However, reports of pollution (abundance of MPs) in river sediments do not consider that the accumulation of sediments and MPs depends on the energy of the river. That is, the abundance of microplastics will be underestimated if the sediments analyzed come from places where the river flows with a lot of energy, and the abundance will be overestimated if the sediment analyzed comes from places where the river flows with less energy. This bias can generate an error greater than 300% of the MPs value reported for the same river and should increase when comparisons are made between 2 rivers with different characteristics. Sections where the river flows with higher energy allow sands to be deposited and limit the accumulation of MPs, while sections, where the same river has lower energy, allow fine sediments such as clays and silts to be deposited and should facilitate the accumulation of MPs particles. That is, the abundance of MPs in the same river is underrepresented when the sediment analyzed is sand, and the abundance of MPs is overrepresented if the sediment analyzed is silt or clay. The present investigation establishes a protocol aimed at incorporating sample granulometry to calibrate MPs quantification and eliminate over- or under-representation bias (hereafter granulometric bias). A total of 30 samples were collected by taking five samples within six work zones. The slope of the sampling points was less than 8 degrees, referred to as low slope areas, according to the Van Zuidam slope classification. During sampling, blanks were used to estimate possible contamination by MPs during sampling. Samples were dried at 60 degrees Celsius for three days. A flotation technique was employed to isolate the MPs using sodium metatungstate with a density of 2 gm/l. For organic matter digestion, 30% hydrogen peroxide and Fenton were used at a ratio of 6:1 for 24 hours. The samples were stained with rose bengal at a concentration of 200 mg/L and were subsequently dried in an oven at 60 degrees Celsius for 1 hour to be identified and photographed in a stereomicroscope with the following conditions: Eyepiece magnification: 10x, Zoom magnification (zoom knob): 4x, Objective lens magnification: 0.35x for analysis in ImageJ. A total of 630 fibers of MPs were identified, mainly red, black, blue, and transparent colors, with an overall average length of 474,310 µm and an overall median length of 368,474 µm. The particle size of the 30 samples was calculated using 100 g per sample using sieves with the following apertures: 2 mm, 1 mm, 500 µm, 250 µm, 125 µm and 0.63 µm. This sieving allowed a visual evaluation and a more precise quantification of the microplastics present. At the same time, the weight of sediment in each fraction was calculated, revealing an evident magnitude: as the presence of sediment in the < 63 µm fraction increases, a significant increase in the number of MPs particles is observed.

Keywords: microplastics, pollution, sediments, Tena River

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Authors: Thelma Maria Melo Pinheiro, Guilherme Raposo Diniz Vieira, Sidney Matos da Silva, Leonardo Mendonça de Oliveira Queiroz, Mateus Sousa Pinheiro, Danyllo Wenceslau de Oliveira Lopes

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The present article has the objective to describe the regulatory impact analysis (RIA) of the contracting efficiency of the Brazilian transmission system usage. This contracting is made by users connected to the main transmission network and is used to guide necessary investments to supply the electrical energy demand. Therefore, an inefficient contracting of this energy amount distorts the real need for grid capacity, affecting the sector planning accuracy and resources optimization. In order to provide this efficiency, the Brazilian Electricity Regulatory Agency (ANEEL) homologated the Normative Resolution (NR) No. 666, from July 23th of 2015, which consolidated the procedures for the contracting of transmission system usage and the contracting efficiency verification. Aiming for a more efficient and rational transmission system contracting, the resolution established economic incentives denominated as Inefficiency installment for excess (IIE) and inefficiency installment for over-contracting (IIOC). The first one, IIE, is verified when the contracted demand exceeds the established regulatory limit; it is applied to consumer units, generators, and distribution companies. The second one, IIOC, is verified when the distributors over-contract their demand. Thus, the establishment of the inefficiency installments IIE and IIOC intends to avoid the agent contract less energy than necessary or more than it is needed. Knowing that RIA evaluates a regulatory intervention to verify if its goals were achieved, the results from the application of the above-mentioned normative resolution to the Brazilian transmission sector were analyzed through indicators that were created for this RIA to evaluate the contracting efficiency transmission system usage, using real data from before and after the homologation of the normative resolution in 2015. For this, indicators were used as the efficiency contracting indicator (ECI), excess of demand indicator (EDI), and over-contracting of demand indicator (ODI). The results demonstrated, through the ECI analysis, a decrease of the contracting efficiency, a behaviour that was happening even before the normative resolution of 2015. On the other side, the EDI showed a considerable decrease in the amount of excess for the distributors and a small reduction for the generators; moreover, the ODI notable decreased, which optimizes the usage of the transmission installations. Hence, with the complete evaluation from the data and indicators, it was possible to conclude that IIE is a relevant incentive for a more efficient contracting, indicating to the agents that their contracting values are not adequate to keep their service provisions for their users. The IIOC also has its relevance, to the point that it shows to the distributors that their contracting values are overestimated.

Keywords: contracting, electricity regulation, evaluation, regulatory impact analysis, transmission power system

Procedia PDF Downloads 102

Authors: Ali Kazemi

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The digital evolution of financial services, while offering unprecedented convenience and accessibility, has also escalated the vulnerabilities to fraudulent activities. In this study, we introduce a distinct approach to real-time anomaly detection in financial transactions, aiming to fortify the defenses of banking and financial institutions against such threats. Utilizing unsupervised machine learning algorithms, specifically autoencoders and isolation forests, our research focuses on identifying irregular patterns indicative of fraud within transactional data, thus enabling immediate action to prevent financial loss. The data we used in this study included the monetary value of each transaction. This is a crucial feature as fraudulent transactions may have distributions of different amounts than legitimate ones, such as timestamps indicating when transactions occurred. Analyzing transactions' temporal patterns can reveal anomalies (e.g., unusual activity in the middle of the night). Also, the sector or category of the merchant where the transaction occurred, such as retail, groceries, online services, etc. Specific categories may be more prone to fraud. Moreover, the type of payment used (e.g., credit, debit, online payment systems). Different payment methods have varying risk levels associated with fraud. This dataset, anonymized to ensure privacy, reflects a wide array of transactions typical of a global banking institution, ranging from small-scale retail purchases to large wire transfers, embodying the diverse nature of potentially fraudulent activities. By engineering features that capture the essence of transactions, including normalized amounts and encoded categorical variables, we tailor our data to enhance model sensitivity to anomalies. The autoencoder model leverages its reconstruction error mechanism to flag transactions that deviate significantly from the learned normal pattern, while the isolation forest identifies anomalies based on their susceptibility to isolation from the dataset's majority. Our experimental results, validated through techniques such as k-fold cross-validation, are evaluated using precision, recall, and the F1 score alongside the area under the receiver operating characteristic (ROC) curve. Our models achieved an F1 score of 0.85 and a ROC AUC of 0.93, indicating high accuracy in detecting fraudulent transactions without excessive false positives. This study contributes to the academic discourse on financial fraud detection and provides a practical framework for banking institutions seeking to implement real-time anomaly detection systems. By demonstrating the effectiveness of unsupervised learning techniques in a real-world context, our research offers a pathway to significantly reduce the incidence of financial fraud, thereby enhancing the security and trustworthiness of digital financial services.

Keywords: anomaly detection, financial fraud, machine learning, autoencoders, isolation forest, transactional data analysis

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Authors: Thomas Larm, Anna Wahlsten

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An international literature study has been carried out for comparison of commonly used methods for the dimensioning of transport systems and stormwater facilities for flow detention. The focus of the literature study regarding the calculation of design flow and detention has been the widely used Rational method and its underlying parameters. The impact of chosen design parameters such as return time, rain intensity, runoff coefficient, and climate factor have been studied. The parameters used in the calculations have been analyzed regarding how they can be calculated and within what limits they can be used. Data used within different countries have been specified, e.g., recommended rainfall return times, estimated runoff times, and climate factors used for different cases and time periods. The literature study concluded that the determination of runoff coefficients is the most uncertain parameter that also affects the calculated flow and required detention volume the most. Proposals have been developed for new runoff coefficients, including a new proposed method with equations for calculating runoff coefficients as a function of return time (years) and rain intensity (l/s/ha), respectively. Suggestions have been made that it is recommended not to limit the use of the Rational Method to a specific catchment size, contrary to what many design manuals recommend, with references to this. The proposed relationships between return time or rain intensity and runoff coefficients need further investigation and to include the quantification of uncertainties. Examples of parameters that have not been considered are the influence on the runoff coefficients of different dimensioning rain durations and the degree of water saturation of green areas, which will be investigated further. The influence of climate effects and design rain on the dimensioning of the stormwater facilities grassed ditches and biofilters (bio retention systems) has been studied, focusing on flow detention capacity. We have investigated how the calculated runoff coefficients regarding climate effect and the influence of changed (increased) return time affect the inflow to and dimensioning of the stormwater facilities. We have developed a smart design of ditches and biofilters that results in both high treatment and flow detention effects and compared these with the effect from dry and wet ponds. Studies of biofilters have generally before focused on treatment of pollutants, but their effect on flow volume and how its flow detention capability can improve is only rarely studied. For both the new type of stormwater ditches and biofilters, it is required to be able to simulate their performance in a model under larger design rains and future climate, as these conditions cannot be tested in the field. The stormwater model StormTac Web has been used on case studies. The results showed that the new smart design of ditches and biofilters had similar flow detention capacity as dry and wet ponds for the same facility area.

Keywords: runoff coefficients, flow detention, smart design, biofilter, ditch

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Authors: Hetvi Trivedi

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Technological escalation cannot be negated. The same is true for the benefits of technology. However, such escalation has interfered with the traditional theories of protection under Intellectual Property Rights. Out of the many trends that have disrupted the old-school understanding of Intellectual Property Rights, one is hashtags. What began modestly in the year 2007 has now earned a remarkable status, and coupled with the unprecedented rise in social media the hashtag culture has witnessed a monstrous growth. A tiny symbol on the keypad of phones or computers is now a major trend which also serves companies as a critical investment measure in establishing their brand in the market. Due to this a section of the Intellectual Property Rights- Trademarks is undergoing a humungous transformation with hashtags like #icebucket, #tbt or #smilewithacoke, getting trademark protection. So, as the traditional theories of IP take on the modern trends, it is necessary to understand the change and challenge at a theoretical and proportional level and where need be, question the change. Traditionally, Intellectual Property Rights serves the societal need for intellectual productions that ensure its holistic development as well as cultural, economic, social and technological progress. In a two-pronged effort at ensuring continuity of creativity, IPRs recognize the investment of individual efforts that go into creation by way of offering protection. Commonly placed under two major theories- Utilitarian and Natural, IPRs aim to accord protection and recognition to an individual’s creation or invention which serve as an incentive for further creations or inventions, thus fully protecting the creative, inventive or commercial labour invested in the same. In return, the creator by lending the public the access to the creation reaps various benefits. This way Intellectual Property Rights form a ‘social contract’ between the author and society. IPRs are similarly attached to a social function, whereby individual rights must be weighed against competing rights and to the farthest limit possible, both sets of rights must be treated in a balanced manner. To put it differently, both the society and the creator must be put on an equal footing with neither party’s rights subservient to the other. A close look through doctrinal research, at the recent trend of trademark protection, makes the social function of IPRs seem to be moving far from the basic philosophy. Thus, where technology interferes with the philosophies of law, it is important to check and allow such growth only in moderation, for none is superior than the other. The human expansionist nature may need everything under the sky that can be tweaked slightly to be counted and protected as Intellectual Property- like a common parlance word transformed into a hashtag, however IP in order to survive on its philosophies needs to strike a balance. A unanimous global decision on the judicious use of IPR recognition and protection is the need of the hour.

Keywords: hashtag trademarks, intellectual property, social function, technology

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Authors: Luis Castiella, Mariano Rueda, Catalina Palacio

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The world’s rapid urbanisation represents an excellent opportunity to implement initiatives that are oriented towards a country’s general development. However, this phenomenon has created considerable pressure on current urban models, pushing them nearer to a crisis. As a result, several factors usually associated with underdevelopment have been steadily rising. Moreover, actions taken by public authorities have not been able to keep up with the speed of urbanisation, which has impeded them from meeting the demands of society, responding with reactionary policies instead of with coordinated, organised efforts. In contrast, the concept of a Smart City which emerged around two decades ago, in principle, represents a city that utilises innovative technologies to remedy the everyday issues of the citizen, empowering them with the newest available technology and information. This concept has come to adopt a wider meaning, including human and social capital, as well as productivity, economic growth, quality of life, environment and participative governance. These developments have also disrupted the management of institutions such as academia, which have become key in generating scientific advancements that can solve pressing problems, and in forming a specialised class that is able to follow up on these breakthroughs. In this light, the Ministry of Modernisation of the Argentinian Nation has created a model that is rooted in the concept of a ‘Smart City’. This effort considered all the dimensions that are at play in an urban environment, with careful monitoring of each sub-dimensions in order to establish the government’s priorities and improving the effectiveness of its operations. In an attempt to ameliorate the overall efficiency of the country’s economic and social development, these focused initiatives have also encouraged citizen participation and the cooperation of the private sector: replacing short-sighted policies with some that are coherent and organised. This process was developed gradually. The first stage consisted in building the model’s structure; the second, at applying the method created on specific case studies and verifying that the mechanisms used respected the desired technical and social aspects. Finally, the third stage consists in the repetition and subsequent comparison of this experiment in order to measure the effects on the ‘treatment group’ over time. The first trial was conducted on 717 municipalities and evaluated the dimension of Governance. Results showed that levels of governmental maturity varied sharply with relation to size: cities with less than 150.000 people had a strikingly lower level of governmental maturity than cities with more than 150.000 people. With the help of this analysis, some important trends and target population were made apparent, which enabled the public administration to focus its efforts and increase its probability of being successful. It also permitted to cut costs, time, and create a dynamic framework in tune with the population’s demands, improving quality of life with sustained efforts to develop social and economic conditions within the territorial structure.

Keywords: composite index, comprehensive model, smart cities, strategic framework

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Authors: Sumeet Rai, Anuj Tyagi, B. T. Naveen Kumar, Shubhkaramjeet Kaur, Niraj K. Singh

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Since their discovery, indiscriminate use of antibiotics in human, veterinary and aquaculture systems has resulted in global emergence/spread of multidrug-resistant bacterial pathogens. Thus, the need for alternative approaches to control bacterial infections has become utmost important. High selectivity/specificity of bacteriophages (phages) permits the targeting of specific bacteria without affecting the desirable flora. In this study, a lytic phage (Ahp1) specific to Aeromonas hydrophila subsp. hydrophila was isolated from finfish aquaculture pond. The host range of Ahp1 range was tested against 10 isolates of A. hydrophila, 7 isolates of A. veronii, 25 Vibrio cholerae isolates, 4 V. parahaemolyticus isolates and one isolate each of V. harveyi and Salmonella enterica collected previously. Except the host A. hydrophila subsp. hydrophila strain, no lytic activity against any other bacterial was detected. During the adsorption rate and one-step growth curve analysis, 69.7% of phage particles were able to get adsorbed on host cell followed by the release of 93 ± 6 phage progenies per host cell after a latent period of ~30 min. Phage nucleic acid was extracted by column purification methods. After determining the nature of phage nucleic acid as dsDNA, phage genome was subjected to next-generation sequencing by generating paired-end (PE, 2 x 300bp) reads on Illumina MiSeq system. De novo assembly of sequencing reads generated circular phage genome of 42,439 bp with G+C content of 58.95%. During open read frame (ORF) prediction and annotation, 22 ORFs (out of 49 total predicted ORFs) were functionally annotated and rest encoded for hypothetical proteins. Proteins involved in major functions such as phage structure formation and packaging, DNA replication and repair, DNA transcription and host cell lysis were encoded by the phage genome. The complete genome sequence of Ahp1 along with gene annotation was submitted to NCBI GenBank (accession number MF683623). Stability of Ahp1 preparations at storage temperatures of 4 °C, 30 °C, and 40 °C was studied over a period of 9 months. At 40 °C storage, phage counts declined by 4 log units within one month; with a total loss of viability after 2 months. At 30 °C temperature, phage preparation was stable for < 5 months. On the other hand, phage counts decreased by only 2 log units over a period of 9 during storage at 4 °C. As some of the phages have also been reported as glycerol sensitive, the stability of Ahp1 preparations in (0%, 15%, 30% and 45%) glycerol stocks were also studied during storage at -80 °C over a period of 9 months. The phage counts decreased only by 2 log units during storage, and no significant difference in phage counts was observed at different concentrations of glycerol. The Ahp1 phage discovered in our study had a very narrow host range and it may be useful for phage typing applications. Moreover, the endolysin and holin genes in Ahp1 genome could be ideal candidates for recombinant cloning and expression of antimicrobial proteins.

Keywords: Aeromonas hydrophila, endolysin, phage, narrow host range

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Authors: Cagri Baris Kasap

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In this study, how interface designers can be viewed as producers of culture in the current era will be interrogated from a critical theory perspective. Walter Benjamin was a German Jewish literary critical theorist who, during 1930s, was engaged in opposing and criticizing the Nazi use of art and media. ‘The Author as Producer’ is an essay that Benjamin has read at the Communist Institute for the Study of Fascism in Paris. In this article, Benjamin relates directly to the dialectics between base and superstructure and argues that authors, normally placed within the superstructure should consider how writing and publishing is production and directly related to the base. Through it, he discusses what it could mean to see author as producer of his own text, as a producer of writing, understood as an ideological construct that rests on the apparatus of production and distribution. So Benjamin concludes that the author must write in ways that relate to the conditions of production, he must do so in order to prepare his readers to become writers and even make this possible for them by engineering an ‘improved apparatus’ and must work toward turning consumers to producers and collaborators. In today’s world, it has become a leading business model within Web 2.0 services of multinational Internet technologies and culture industries like Amazon, Apple and Google, to transform readers, spectators, consumers or users into collaborators and co-producers through platforms such as Facebook, YouTube and Amazon’s CreateSpace Kindle Direct Publishing print-on-demand, e-book and publishing platforms. However, the way this transformation happens is tightly controlled and monitored by combinations of software and hardware. In these global-market monopolies, it has become increasingly difficult to get insight into how one’s writing and collaboration is used, captured, and capitalized as a user of Facebook or Google. In the lens of this study, it could be argued that this criticism could very well be considered by digital producers or even by the mass of collaborators in contemporary social networking software. How do software and design incorporate users and their collaboration? Are they truly empowered, are they put in a position where they are able to understand the apparatus and how their collaboration is part of it? Or has the apparatus become a means against the producers? Thus, when using corporate systems like Google and Facebook, iPhone and Kindle without any control over the means of production, which is closed off by opaque interfaces and licenses that limit our rights of use and ownership, we are already the collaborators that Benjamin calls for. For example, the iPhone and the Kindle combine a specific use of technology to distribute the relations between the ‘authors’ and the ‘prodUsers’ in ways that secure their monopolistic business models by limiting the potential of the technology.

Keywords: interface designer, cultural producer, Walter Benjamin, materialist aesthetics, dialectical thinking

Procedia PDF Downloads 126

Authors: Majid Farsadrouh Rashti, Alireza Mohammadinejad, Amir Shafiee Kisomi

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Lead (Pb²⁺), a cation, is a prime constituent of the majority of the industrial effluents such as mining, smelting and coal combustion, Pb-based painting and Pb containing pipes in water supply systems, paper and pulp refineries, printing, paints and pigments, explosive manufacturing, storage batteries, alloy and steel industries. The maximum permissible limit of lead in the water used for drinking and domesticating purpose is 0.01 mg/L as advised by Bureau of Indian Standards, BIS. This becomes the acceptable 'safe' level of lead(II) ions in water beyond which, the water becomes unfit for human use and consumption, and is potential enough to lead health problems and epidemics leading to kidney failure, neuronal disorders, and reproductive infertility. Superabsorbent hydrogels are loosely crosslinked hydrophilic polymers that in contact with aqueous solution can easily water and swell to several times to their initial volume without dissolving in aqueous medium. Superabsorbents are kind of hydrogels capable to swell and absorb a large amount of water in their three-dimensional networks. While the shapes of hydrogels do not change extensively during swelling, because of tremendously swelling capacity of superabsorbent, their shape will broadly change.Because of their superb response to changing environmental conditions including temperature pH, and solvent composition, superabsorbents have been attracting in numerous industrial applications. For instance, water retention property and subsequently. Natural-based superabsorbent hydrogels have attracted much attention in medical pharmaceutical, baby diapers, agriculture, and horticulture because of their non-toxicity, biocompatibility, and biodegradability. Novel superabsorbent hydrogel nanocomposites were prepared by graft copolymerization of acrylamide and itaconic acid in the presence of nanoclay (laponite), using methylene bisacrylamide (MBA) and potassium persulfate, former as a crosslinking agent and the second as an initiator. The superabsorbent hydrogel nanocomposites structure was characterized by FTIR spectroscopy, SEM and TGA Spectroscopy adsorption of metal ions on poly (AAm-co-IA). The equilibrium swelling values of copolymer was determined by gravimetric method. During the adsorption of metal ions on polymer, residual metal ion concentration in the solution and the solution pH were measured. The effects of the clay content of the hydrogel on its metal ions uptake behavior were studied. The NC hydrogels may be considered as a good candidate for environmental applications to retain more water and to remove heavy metals.

Keywords: adsorption, hydrogel, nanocomposite, super adsorbent

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Authors: Andrew N. Saylor, James R. Peters

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Scoliosis is a complex 3D deformity of the thoracic and lumbar spines, clinically diagnosed by measurement of a Cobb angle of 10 degrees or more on a coronal X-ray. The Cobb angle is the angle made by the lines drawn along the proximal and distal endplates of the respective proximal and distal vertebrae comprising the curve. Traditionally, Cobb angles are measured manually using either a marker, straight edge, and protractor or image measurement software. The task of measuring the Cobb angle can also be represented by a function taking the spine geometry rendered using X-ray imaging as input and returning the approximate angle. Although the form of such a function may be unknown, it can be approximated using artificial neural networks (ANNs). The performance of ANNs is affected by many factors, including the choice of activation function and network architecture; however, the effects of these parameters on the accuracy of scoliotic deformity measurements are poorly understood. Therefore, the objective of this study was to systematically investigate the effect of ANN architecture and activation function on Cobb angle measurement from the coronal X-rays of scoliotic subjects. The data set for this study consisted of 609 coronal chest X-rays of scoliotic subjects divided into 481 training images and 128 test images. These data, which included labeled Cobb angle measurements, were obtained from the SpineWeb online database. In order to normalize the input data, each image was resized using bi-linear interpolation to a size of 500 × 187 pixels, and the pixel intensities were scaled to be between 0 and 1. A fully connected (dense) ANN with a fixed cost function (mean squared error), batch size (10), and learning rate (0.01) was developed using Python Version 3.7.3 and TensorFlow 1.13.1. The activation functions (sigmoid, hyperbolic tangent [tanh], or rectified linear units [ReLU]), number of hidden layers (1, 3, 5, or 10), and number of neurons per layer (10, 100, or 1000) were varied systematically to generate a total of 36 network conditions. Stochastic gradient descent with early stopping was used to train each network. Three trials were run per condition, and the final mean squared errors and mean absolute errors were averaged to quantify the network response for each condition. The network that performed the best used ReLU neurons had three hidden layers, and 100 neurons per layer. The average mean squared error of this network was 222.28 ± 30 degrees2, and the average mean absolute error was 11.96 ± 0.64 degrees. It is also notable that while most of the networks performed similarly, the networks using ReLU neurons, 10 hidden layers, and 1000 neurons per layer, and those using Tanh neurons, one hidden layer, and 10 neurons per layer performed markedly worse with average mean squared errors greater than 400 degrees2 and average mean absolute errors greater than 16 degrees. From the results of this study, it can be seen that the choice of ANN architecture and activation function has a clear impact on Cobb angle inference from coronal X-rays of scoliotic subjects.

Keywords: scoliosis, artificial neural networks, cobb angle, medical imaging

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Authors: Tan Hui Ying Renee, Stella Rizalina Sasha, Farah Safdar Husain

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Introduction: Menopause Hormone Therapy (MHT) is an effective drug indicated for the treatment of menopausal symptoms and as replacement therapy in women who undergo premature menopause. In 2020, less than 8.8% of perimenopausal Singaporean women are on hormonal therapy, as compared to the Western population, where up to 50% may be on MHT. Factors associated with MHT utilization have been studied from patient characteristics, but the impact of locally prescribing physicians resulting in low MHT utilization has yet to be evaluated. The aim of the study is to determine the level of knowledge physicians in the Obstetrics and Gynaecology specialty have and their attitudes toward MHT. We believe that knowledge of MHT is lacking and that negative attitudes towards MHT may influence its use and undermine the benefits MHT may have for women. This paper is a part of a larger study on Singaporean physicians’ knowledge and attitudes towards MHT. Methods: This is a cross-sectional study intended to assess the knowledge and attitudes of physicians toward Menopausal Hormone Therapy. An anonymous questionnaire was disseminated via institutional internal circulations to optimize reach to physicians who may prescribe MHT, particularly in the fields of Gynaecology, Family Medicine and Endocrinology. Responses were completed voluntarily. Physicians had the option for each question to declare that they were ‘unsure’ or that the question was ‘beyond their expertise’. 21 knowledge questions tested factual recall on indications, contraindications, and risks of MHT. The remaining 6 questions were clinical scenarios crafted with the intention of testing specific principles related to the use of MHT. These questions received face validation from experts in the field. 198 responses were collected, 79 of which were from physicians in the Obstetrics and Gynaecology specialty. The data will be statistically analyzed to investigate areas that can be improved to increase the overall benefits of MHT for the Singaporean population. Results: Preliminary results show that the prevailing factors that limit Singaporean gynecologists and obstetricians from prescribing MHT are a lack of knowledge of MHT and a lack of confidence in prescribing MHT. Risks and indications of MHT were not well known by many physicians, with the majority of the questions having more than 25% incorrect and ‘unsure’ as their reply. The clinical scenario questions revealed significant shortcomings in knowledge on how to navigate real-life challenges in MHT use, with 2 of 6 questions with more than 50% incorrect or ‘beyond their expertise’ as their reply. The portion of the questionnaire that investigated the attitudes of physicians showed that though a large majority believed MHT to be an effective drug, only 40.5% were confident in prescribing it. Conclusion: Physicians in the Obstetrics and Gynaecology specialty lack knowledge and confidence in MHT. Therefore, it is imperative to formulate solutions on both the individual and institutional levels to fill these gaps and ensure that MHT is used appropriately and prescribed to the patients who need it.

Keywords: menopause, menopause hormone therapy, physician factors, obstetrics and gynecology, menopausal symptoms, Singapore

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Authors: Raptis Sotirios

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Health and social care (HSc) services planning and scheduling are facing unprecedented challenges due to the pandemic pressure and also suffer from unplanned spending that is negatively impacted by the global financial crisis. Data-driven can help to improve policies, plan and design services provision schedules using algorithms assist healthcare managers’ to face unexpected demands using fewer resources. The paper discusses services packing using statistical significance tests and machine learning (ML) to evaluate demands similarity and coupling. This is achieved by predicting the range of the demand (class) using ML methods such as CART, random forests (RF), and logistic regression (LGR). The significance tests Chi-Squared test and Student test are used on data over a 39 years span for which HSc services data exist for services delivered in Scotland. The demands are probabilistically associated through statistical hypotheses that assume that the target service’s demands are statistically dependent on other demands as a NULL hypothesis. This linkage can be confirmed or not by the data. Complementarily, ML methods are used to linearly predict the above target demands from the statistically found associations and extend the linear dependence of the target’s demand to independent demands forming, thus groups of services. Statistical tests confirm ML couplings making the prediction also statistically meaningful and prove that a target service can be matched reliably to other services, and ML shows these indicated relationships can also be linear ones. Zero paddings were used for missing years records and illustrated better such relationships both for limited years and in the entire span offering long term data visualizations while limited years groups explained how well patients numbers can be related in short periods or can change over time as opposed to behaviors across more years. The prediction performance of the associations is measured using Receiver Operating Characteristic(ROC) AUC and ACC metrics as well as the statistical tests, Chi-Squared and Student. Co-plots and comparison tables for RF, CART, and LGR as well as p-values and Information Exchange(IE), are provided showing the specific behavior of the ML and of the statistical tests and the behavior using different learning ratios. The impact of k-NN and cross-correlation and C-Means first groupings is also studied over limited years and the entire span. It was found that CART was generally behind RF and LGR, but in some interesting cases, LGR reached an AUC=0 falling below CART, while the ACC was as high as 0.912, showing that ML methods can be confused padding or by data irregularities or outliers. On average, 3 linear predictors were sufficient, LGR was found competing RF well, and CART followed with the same performance at higher learning ratios. Services were packed only if when significance level(p-value) of their association coefficient was more than 0.05. Social factors relationships were observed between home care services and treatment of old people, birth weights, alcoholism, drug abuse, and emergency admissions. The work found that different HSc services can be well packed as plans of limited years, across various services sectors, learning configurations, as confirmed using statistical hypotheses.

Keywords: class, cohorts, data frames, grouping, prediction, prob-ability, services

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Authors: Tin Yee Ling, Kavita Maravar, Ruzica Ardalic

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Background: Uterine torsion (UT) in pregnancy of more than 45-degree along the longitudinal axis is a rare occurrence, and the aetiology remains unclear. Case: A 34-year-old G2P1 woman with a history of one previous caesarean section presented at 36+2 weeks with sudden onset lower abdominal pain, syncopal episode, and tender abdomen on examination. She was otherwise haemodynamically stable. Cardiotocography showed a pathological trace with initial prolonged bradycardia followed by a subsequent tachycardia with reduced variability. An initial diagnosis of uterine dehiscence was made, given the history and clinical presentation. She underwent an emergency caesarean section which revealed a 180-degree UT along the longitudinal axis, with oedematous left round ligament lying transverse anterior to the uterus and a segment of large bowel inferior to the round ligament. Detorsion of uterus was performed prior to delivery of the foetus, and anterior uterine wall was intact with no signs of rupture. There were no anatomical uterine abnormalities found other than stretched left ovarian and round ligaments, which were repaired. Delivery was otherwise uneventful, and she was discharged on day 2 postpartum. Discussion: UT is rare as the number of reported cases is within the few hundreds worldwide. Generally, the uterus is supported in place by uterine ligaments, which limit the mobility of the structure. The causes of UT are unknown, but risk factors such as uterine abnormalities, increased uterine ligaments’ flexibility in pregnancy, and foetal malposition has been identified. UT causes occlusion of uterine vessels, which can lead to ischaemic injury of the placenta causing premature separation of the placenta, preterm labour, and foetal morbidity and mortality if delivery is delayed. Diagnosing UT clinically is difficult as most women present with symptoms similar to placenta abruption or uterine rupture (abdominal pain, vaginal bleeding, shock), and one-third are asymptomatic. The management of UT involves surgical detorsion of the uterus and delivery of foetus via caesarean section. Extra vigilance should be taken to identify the anatomy of the uterus experiencing torsion prior to hysterotomy. There have been a few cases reported with hysterotomy on posterior uterine wall for delivery of foetus as it may be difficult to identify and reverse a gravid UT when foetal well-being is at stake. Conclusion: UT should be considered a differential diagnosis of acute abdominal pain in pregnancy. It is crucial that the torsion is addressed immediately as it is associated with maternal and foetal morbidity and mortality.

Keywords: uterine torsion, pregnancy complication, abdominal pain, torted uterus

Procedia PDF Downloads 139

Authors: Collen T. Masilo, Brane Semolic, Pieter Steyn

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The Internet Protocol Television (IPTV) and Hybrid Fibre-Coaxial (HFC) Broadband industrial sector landscape are rapidly changing and organisations within the industry need to stay competitive by exploring new business models so that they can be able to offer new services and products to customers. The business challenge in this industrial sector is meeting or exceeding high customer expectations across multiple content delivery modes. The increasing challenges in the IPTV and HFC broadband industrial sector encourage service providers to form strategic partnerships with key suppliers, marketing partners, advertisers, and technology partners. The need to form enterprise collaborative networks poses a challenge for any organisation in this sector, in selecting the right strategic partners who will ensure that the organisation’s services and products are marketed in new markets. Partners who will ensure that customers are efficiently supported by meeting and exceeding their expectations. Lastly, selecting cooperation partners who will represent the organisation in a positive manner, and contribute to improving the performance of the organisation. Companies in the IPTV and HFC broadband industrial sector tend to form informal partnerships with suppliers, vendors, system integrators and technology partners. Generally, partnerships are formed without thorough analysis of the real reason a company is forming collaborations, without proper evaluations of prospective partners using specific selection criteria, and with ineffective performance monitoring of partners to ensure that a firm gains real long term benefits from its partners and gains competitive advantage. Similar tendencies are illustrated in the research case study and are based on Skyline Communications, a global leader in end-to-end, multi-vendor network management and operational support systems (OSS) solutions. The organisation’s flagship product is the DataMiner network management platform used by many operators across multiple industries and can be referred to as a smart system that intelligently manages complex technology ecosystems for its customers in the IPTV and HFC broadband industry. The approach of the research is to develop the most efficient business model that can be deployed to improve a strategic partnership programme in order to significantly improve the performance and growth of organisations participating in a collaborative network in the IPTV and HFC broadband industrial sector. This involves proposing and implementing a new strategic partnership model and its main features within the industry which should bring about significant benefits for all involved companies to achieve value add and an optimal growth strategy. The proposed business model has been developed based on the research of existing relationships, value chains and business requirements in this industrial sector and validated in 'Skyline Communications'. The outputs of the business model have been demonstrated and evaluated in the research business case study the IPTV and HFC broadband service provider 'Skyline Communications'.

Keywords: growth, partnership, selection criteria, value chain

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Authors: Utpal Das, Sona Das

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InAs/GaSb type-II superlattice (T2SL) Mid-wave infrared (MWIR) focal plane arrays (FPAs) have recently seen rapid development. However, in small pixel size large format FPAs, the occurrence of high mesa sidewall surface leakage current is a major constraint necessitating proper surface passivation. A simple pixel isolation technique in InAs/GaSb T2SL detector arrays without the conventional mesa etching has been proposed to isolate the pixels by forming a more resistive higher band gap material from the SL, in the inter-pixel region. Here, a single step femtosecond (fs) laser anneal of the T2SL structure of the inter-pixel T2SL regions, have been used to increase the band gap between the pixels by QW-intermixing and hence increase isolation between the pixels. The p-i-n photodiode structure used here consists of a 506nm, (10 monolayer {ML}) InAs:Si (1x10¹⁸cm⁻³)/(10ML) GaSb SL as the bottom n-contact layer grown on an n-type GaSb substrate. The undoped absorber layer consists of 1.3µm, (10ML)InAs/(10ML)GaSb SL. The top p-contact layer is a 63nm, (10ML)InAs:Be(1x10¹⁸cm⁻³)/(10ML)GaSb T2SL. In order to improve the carrier transport, a 126nm of graded doped (10ML)InAs/(10ML)GaSb SL layer was added between the absorber and each contact layers. A 775nm 150fs-laser at a fluence of ~6mJ/cm² is used to expose the array where the pixel regions are masked by a Ti(200nm)-Au(300nm) cap. Here, in the inter-pixel regions, the p+ layer have been reactive ion etched (RIE) using CH₄+H₂ chemistry and removed before fs-laser exposure. The fs-laser anneal isolation improvement in 200-400μm pixels due to spatially selective quantum well intermixing for a blue shift of ~70meV in the inter-pixel regions is confirmed by FTIR measurements. Dark currents are measured between two adjacent pixels with the Ti(200nm)-Au(300nm) caps used as contacts. The T2SL quality in the active photodiode regions masked by the Ti-Au cap is hardly affected and retains the original quality of the detector. Although, fs-laser anneal of p+ only etched p-i-n T2SL diodes show a reduction in the reverse dark current, no significant improvement in the full RIE-etched mesa structures is noticeable. Hence for a 128x128 array fabrication of 8μm square pixels and 10µm pitch, SU8 polymer isolation after RIE pixel delineation has been used. X-n+ row contacts and Y-p+ column contacts have been used to measure the optical response of the individual pixels. The photo-response of these 8μm and other 200μm pixels under a 2ns optical pulse excitation from an Optical-Parametric-Oscillator (OPO), shows a peak responsivity of ~0.03A/W and 0.2mA/W, respectively, at λ~3.7μm. Temporal response of this detector array is seen to have a fast response ~10ns followed typical slow decay with ringing, attributed to impedance mismatch of the connecting co-axial cables. In conclusion, response times of a few ns have been measured in 8µm pixels of a 128x128 array. Although fs-laser anneal has been found to be useful in increasing the inter-pixel isolation in InAs/GaSb T2SL arrays by QW inter-mixing, it has not been found to be suitable for passivation of full RIE etched mesa structures with vertical walls on InAs/GaSb T2SL.

Keywords: band-gap blue-shift, fs-laser-anneal, InAs/GaSb T2SL, Inter-pixel isolation, ns-Response, photodiode array

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Authors: Sara E. Baumann, Megan A. Rabin, Mary Hawk, Bhimsen Devkota, Kajol Upadhyaya, Guna Raj Shrestha, Brigit Joseph, Annika Agarwal, Jessica G. Burke

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In Nepal, prevailing sociocultural norms associated with menstruation prompt adherence to stringent rules that limit participation in daily activities. Chhaupadi is a specific menstrual tradition in Nepal in which women and girls segregate themselves and follow a series of restrictions during menstruation. Despite having numerous physical and mental health implications, extant interventions have yet to sustainably address the harms associated with chhaupadi. In this study, the authors describe insights garnered from a collaboration with community members in Dailekh district, who formulated their own approaches to mitigate the adverse facets of chhaupadi. Envisaged as an entry point to improve women’s menstrual health experiences, this investigation employed an approach that uses Human-centered Design and a community-engaged approach. The authors conducted a four-day design workshop which unfolded in two phases: The Discovery Phase, to uncover chhaupadi context and key stakeholders, and the Design Phase, to design contextually relevant interventions. Diverse community-members, including those with lived experience practicing chhaupadi, developed five intervention concepts: 1) harnessing Female Community Health Volunteers as role models, for counseling, and raising awareness; 2) focusing on mothers and mother’s groups to instigate behavioral shifts; 3) engaging the broader community in behavior change efforts; 4) empowering fathers to effect change in their homes through counseling and education; and 5) training and emboldening youth to advocate for positive change through advocacy in their schools and homes. This research underscores the importance of employing multi-level approaches tailored to specific stakeholder groups, given Nepal’s rich cultural diversity. The engagement of Female Community Health Volunteers emerged as a promising yet underexplored intervention concept for chhaupadi, warranting broader implementation. Crucially, it is also imperative for interventions to prioritize tackling deleterious aspects of the chhaupadi tradition, emphasizing safety considerations, all while acknowledging chhaupadi’s entrenched cultural history; for some, there are positive aspects of the tradition that women and girls wish to preserve.

Keywords: human-centered design, menstrual health, Nepal, community-engagement, intervention development, women's health, rural health

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Authors: Thomas Folegot, Arnaud Levaufre, Léna Bourven, Nicolas Kermagoret, Alexis Caillard, Roger Gallou

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Concern for negative impacts of anthropogenic noise on the ocean’s ecosystems has increased over the recent decades. This concern leads to a similar increased willingness to regulate noise-generating activities, of which shipping is one of the most significant. Dealing with ship noise requires not only knowledge about the noise from individual ships, but also how the ship noise is distributed in time and space within the habitats of concern. Marine mammals, but also fish, sea turtles, larvae and invertebrates are mostly dependent on the sounds they use to hunt, feed, avoid predators, during reproduction to socialize and communicate, or to defend a territory. In the marine environment, sight is only useful up to a few tens of meters, whereas sound can propagate over hundreds or even thousands of kilometers. Directive 2008/56/EC of the European Parliament and of the Council of June 17, 2008 called the Marine Strategy Framework Directive (MSFD) require the Member States of the European Union to take the necessary measures to reduce the impacts of maritime activities to achieve and maintain a good environmental status of the marine environment. The Ocean-Planner is a web-based platform that provides to regulators, managers of protected or sensitive areas, etc. with a decision support tool that enable to anticipate and quantify the effectiveness of management measures in terms of reduction or modification the distribution of underwater noise, in response to Descriptor 11 of the MSFD and to the Marine Spatial Planning Directive. Based on the operational sound modelling tool Quonops Online Service, Ocean-Planner allows the user via an intuitive geographical interface to define management measures at local (Marine Protected Area, Natura 2000 sites, Harbors, etc.) or global (Particularly Sensitive Sea Area) scales, seasonal (regulation over a period of time) or permanent, partial (focused to some maritime activities) or complete (all maritime activities), etc. Speed limit, exclusion area, traffic separation scheme (TSS), and vessel sound level limitation are among the measures supported be the tool. Ocean Planner help to decide on the most effective measure to apply to maintain or restore the biodiversity and the functioning of the ecosystems of the coastal seabed, maintain a good state of conservation of sensitive areas and maintain or restore the populations of marine species.

Keywords: underwater noise, marine biodiversity, marine spatial planning, mitigation measures, prediction

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Authors: El Hadji Mamadou Sonko, Mbaye Mbéguéré, Cheikh Diop, Linda Strande

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In new approaches that are being developed for the treatment of sludge, the valorization of by-product is increasingly encouraged. In this perspective, Echinochloa pyramidalis has been successfully tested in Cameroon. Echinochloa pyramidalis is an efficient forage plant in the treatment of faecal sludge. It provides high removal rates and biosolids of high agronomic value. Thus in order to advise the use of this plant in planted drying beds in Senegal its comparison with the plants long been used in the field deserves to be carried out. That is the aim of this study showing the influence of the nature of the plants on the drainage, the purifying performances and the quality of the biosolids. Echinochloa pyramidalis, Typha australis, and Phragmites australis are the three macrophytes used in this study. The drainage properties of the beds were monitored through the frequency of clogging, the percentage of recovered leachate and the dryness of the accumulated sludge. The development of plants was followed through the measurement of the density. The purification performances were evaluated from the incoming raw sludge flows and the outflows of leachate for parameters such as Total Solids (TS), Total Suspended Solids (TSS), Total Volatile Solids (TVS), Chemical Oxygen Demand (COD), Total Kjeldahl Nitrogen (TKN), Ammonia (NH₄⁺), Nitrate (NO₃⁻), Total Phosphorus (TP), Orthophosphorus (PO₄³⁻) and Ascaris eggs. The quality of the biosolids accumulated on the beds was measured after 3 months of maturation for parameters such as dryness, C/N ratio NH₄⁺/NO₃⁻ ratio, ammonia, Ascaris eggs. The results have shown that the recovered leachate volume is about 40.4%; 45.6% and 47.3%; the dryness about 41.7%; 38.7% and 28.7%, and clogging frequencies about 6.7%; 8.2% and 14.2% on average for the beds planted with Echinochloa pyramidalis, Typha australis and Phragmites australis respectively. The plants of Echinochloa pyramidalis (198.6 plants/m²) and Phragmites australis (138 plants/m²) have higher densities than Typha australis (90.3 plants/m²). The nature of the plants has no influence on the purification performance with reduction percentages around 80% or more for all the parameters followed whatever the nature of the plants. However, the concentrations of these various leachate pollutants are above the limit values of the Senegalese standard NS 05-061 for the release into the environment. The biosolids harvested after 3 months of maturation are all mature with C/N ratios around 10 for all the macrophytes. The NH₄⁺/NO₃⁻ ratio is lower than 1 except for the biosolids originating from the Echinochloa pyramidalis beds. The ammonia is also less than 0.4 g/kg except for biosolids from Typha australis beds. Biosolids are also rich in mineral elements. Their concentrations of Ascaris eggs are higher than the WHO recommendations despite a percentage of inactivation around 80%. These biosolids must be stored for an additional time or composted. From these results, the use of Echinochloa pyramidalis as the main macrophyte can be recommended in the various drying beds planted in sub-Saharan climate conditions.

Keywords: faecal sludge, nature of plants, quality of biosolids, treatment performances

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Authors: Glauco M. M. M. Lustosa, João Paulo C. Costa, Leinig Antônio Perazolli, Maria Aparecida Zaghete

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SnO2 has electrical conductivity due to the excess of electrons and structural defects, being its electrical behavior highly dependent on sintering temperature and chemical composition. The addition of metals modifiers into the crystalline structure can improve and controlling the behavior of some semiconductor oxides that can therefore develop different applications such as varistors (ceramic with non-ohmic behavior between current and voltage, i.e. conductive during normal operation and resistive during overvoltage). The polymeric precursor method, based on the complexation reaction between metal ion and policarboxylic acid and then polymerized with ethylene glycol, was used to obtain nanopowders ceramic. The metal immobilization reduces its segregation during the decomposition of the polyester resulting in a crystalline oxide with high chemical homogeneity. The preparation of films from ceramics nanoparticles using electrophoretic deposition method (EPD) brings prospects for a new generation of smaller size devices with easy integration technology. EPD allows to control time and current and therefore it can have control of the thickness, surface roughness and the film density, quickly and with low production costs. The sintering process is key to control size and grain boundary density of the film. In this step, there is the diffusion of metals that promote densification and control of intrinsic defects or change these defects which will form and modify the potential barrier in the grain boundary. The use of microwave oven for sintering is an advantageous process due to the fast and homogeneous heating rate, promoting the diffusion and densification without irregular grain growth. This research was done a comparative study of sintering temperature by use of zinc as modifier agent to verify the influence on sintering step aiming to promote densification and grain growth, which influences the potential barrier formation and then changed the electrical behavior. SnO2-nanoparticles were obtained with 1 %mol of ZnO + 0.05 %mol of Nb2O5 (SZN), deposited as film through EPD (voltage 2 kV, time of 10 min) on Si/Pt substrate. Sintering was made in a microwave oven at 800, 900 and 1000 °C. For complete coverage of the substrate by nanoparticles with low surface roughness and uniform thickness was added 0.02 g of solid iodine in alcoholic suspension SnO2 to increase particle surface charge. They were also used magneto in EPD system that improved the deposition rate forming a compact film. Using a scanning electron microscope of high resolution (SEM_FEG) it was observed nanoparticles with average size between 10-20 nm, after sintering the average size was 150 to 200 nm and thickness of 5 µm. Also, it was verified that the temperature at 1000 °C was the most efficient in sintering. The best sintering time was also recorded and determined as 40 minutes. After sintering, the films were recovered with Cr3+ ions layer by EPD, then the films were again thermally treated. The electrical characterizations (nonlinear coefficient of 11.4, voltage rupture of ~60 V and leakage current = 4.8x10−6 A), allow considering the new methodology suitable for prepare SnO2-based varistor applied for development of electrical protection devices for low voltage.

Keywords: chemical synthesis, electrophoretic deposition, microwave sintering, tin dioxide

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Authors: Elisa Esposito, Johannes C. Jansen, Loredana Dellamuzia, Ugo Moretti, Lidietta Giorno

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The reduction of CO₂ emission into the atmosphere as a result of human activity is one of the most important environmental challenges to face in the next decennia. Emission of CO₂, related to the use of fossil fuels, is believed to be one of the main causes of global warming and climate change. In this scenario, the production of biomethane from organic waste, as a renewable energy source, is one of the most promising strategies to reduce fossil fuel consumption and greenhouse gas emission. Unfortunately, biogas upgrading still produces the greenhouse gas CO₂ as a waste product. Therefore, this work presents a case study on biogas upgrading, aimed at the simultaneous purification of methane and CO₂ via different steps, including CO₂/methane separation by polymeric membranes. The original objective of the project was the biogas upgrading to distribution grid quality methane, but the innovative aspect of this case study is the further purification of the captured CO₂, transforming it from a useless by-product to a pure gas with food-grade quality, suitable for commercial application in the food and beverage industry. The study was performed on a pilot plant constructed by Tecno Project Industriale Srl (TPI) Italy. This is a model of one of the largest biogas production and purification plants. The full-scale anaerobic digestion plant (Montello Spa, North Italy), has a digestive capacity of 400.000 ton of biomass/year and can treat 6.250 m3/hour of biogas from FORSU (organic fraction of solid urban waste). The entire upgrading process consists of a number of purifications steps: 1. Dehydration of the raw biogas by condensation. 2. Removal of trace impurities such as H₂S via absorption. 3.Separation of CO₂ and methane via a membrane separation process. 4. Removal of trace impurities from CO₂. The gas separation with polymeric membranes guarantees complete simultaneous removal of microorganisms. The chemical purity of the different process streams was analysed by a certified laboratory and was compared with the guidelines of the European Industrial Gases Association and the International Society of Beverage Technologists (EIGA/ISBT) for CO₂ used in the food industry. The microbiological purity was compared with the limit values defined in the European Collaborative Action. With a purity of 96-99 vol%, the purified methane respects the legal requirements for the household network. At the same time, the CO₂ reaches a purity of > 98.1% before, and 99.9% after the final distillation process. According to the EIGA/ISBT guidelines, the CO₂ proves to be chemically and microbiologically sufficiently pure to be suitable for food-grade applications.

Keywords: biogas, CO₂ separation, CO2 utilization, CO₂ food grade

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Authors: Marcin Debowski, Marcin Zielinski, Magdalena Zielinska, Paulina Rusanowska

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The problem with digestate management is one of the most important factors influencing on the development and operation of biogas plant. Turbidity and bacterial contamination negatively affect the growth of algae, which can limit the use of the effluent in the production of algae biomass on a large scale. These problems can be overcome by cultivating of algae species resistant to environmental factors, such as Chlorella sp., Scenedesmus sp., or reducing load of organic compounds to prevent bacterial contamination. The effluent requires dilution and/or purification. One of the methods of effluent treatment is the use of a membrane technology such as microfiltration (MF), ultrafiltration (UF), nanofiltration (NF) and reverse osmosis (RO), depending on the membrane pore size and the cut off point. Membranes are a physical barrier to solids and particles larger than the size of the pores. MF membranes have the largest pores and are used to remove turbidity, suspensions, bacteria and some viruses. UF membranes remove also color, odor and organic compounds with high molecular weight. In treatment of wastewater or other waste streams, MF and UF can provide a sufficient degree of purification. NF membranes are used to remove natural organic matter from waters, water disinfection products and sulfates. RO membranes are applied to remove monovalent ions such as Na⁺ or K⁺. The effluent was used in UF for medium to cultivation of two microalgae: Chlorella sp. and Phaeodactylum tricornutum. Growth rates of Chlorella sp. and P. tricornutum were similar: 0.216 d⁻¹ and 0.200 d⁻¹ (Chlorella sp.); 0.128 d⁻¹ and 0.126 d⁻¹ (P. tricornutum), on synthetic medium and permeate from UF, respectively. The final biomass composition was also similar, regardless of the medium. Removal of nitrogen was 92% and 71% by Chlorella sp. and P. tricornutum, respectively. The fermentation effluents after UF and dilution were also used for cultivation of algae Scenedesmus sp. that is resistant to environmental conditions. The authors recommended the development of biorafinery based on the production of algae for the biogas production. There are examples of using a multi-stage membrane system to purify the liquid fraction from digestate. After the initial UF, RO is used to remove ammonium nitrogen and COD. To obtain a permeate with a concentration of ammonium nitrogen allowing to discharge it into the environment, it was necessary to apply three-stage RO. The composition of the permeate after two-stage RO was: COD 50–60 mg/dm³, dry solids 0 mg/dm³, ammonium nitrogen 300–320 mg/dm³, total nitrogen 320–340 mg/dm³, total phosphorus 53 mg/dm³. However compostion of permeate after three-stage RO was: COD < 5 mg/dm³, dry solids 0 mg/dm³, ammonium nitrogen 0 mg/dm³, total nitrogen 3.5 mg/dm³, total phosphorus < 0,05 mg/dm³. Last stage of RO might be replaced by ion exchange process. The negative aspect of membrane filtration systems is the fact that the permeate is about 50% of the introduced volume, the remainder is the retentate. The management of a retentate might involve recirculation to a biogas plant.

Keywords: digestate, membrane filtration, microalgae cultivation, Chlorella sp.

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Authors: Candy Chieh Lee

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Objective: The purpose of this study is to investigate the relationship between visual perception and social function in patients with schizophrenia. The specific aims are: 1) To explore performances in visual perception and social function in patients with schizophrenia 2) to examine the correlation between visual perceptual skills and social function in patients with schizophrenia The long-term goal is to be able to provide the most adequate intervention program for promoting patients’ visual perceptual skills and social function, as well as compensatory techniques. Background: Perceptual deficits in schizophrenia have been well documented in the visual system. Clinically, a considerable portion (up to 60%) of schizophrenia patients report distorted visual experiences such as visual perception of motion, color, size, and facial expression. Visual perception is required for the successful performance of most activities of daily living, such as dressing, making a cup of tea, driving a car and reading. On the other hand, patients with schizophrenia usually exhibit psychotic symptoms such as auditory hallucination and delusions which tend to alter their perception of reality and affect their quality of interpersonal relationship and limit their participation in various social situations. Social function plays an important role in the prognosis of patients with schizophrenia; lower social functioning skills can lead to poorer prognosis. Investigations on the relationship between social functioning and perceptual ability in patients with schizophrenia are relatively new but important as the results could provide information for effective intervention on visual perception and social functioning in patients with schizophrenia. Methods: We recruited 50 participants with schizophrenia in the mental health hospital (Taipei City Hospital, Songde branch, Taipei, Taiwan) acute ward. Participants who have signed consent forms, diagnosis of schizophrenia and having no organic vision deficits were included. Participants were administered the test of visual-perceptual skills (non-motor), third edition (TVPS-3) and the personal and social performance scale (PSP) for assessing visual perceptual skill and social function. The assessments will take about 70-90 minutes to complete. Data Analysis: The IBM SPSS 21.0 will be used to perform the statistical analysis. First, descriptive statistics will be performed to describe the characteristics and performance of the participants. Lastly, Pearson correlation will be computed to examine the correlation between PSP and TVPS-3 scores. Results: Significant differences were found between the means of participants’ TVPS-3 raw scores of each subtest with the age equivalent raw score provided by the TVPS-3 manual. Significant correlations were found between all 7 subtests of TVPS-3 and PSP total score. Conclusions: The results showed that patients with schizophrenia do exhibit visual perceptual deficits and is correlated social functions. Understanding these facts of patients with schizophrenia can assist health care professionals in designing and implementing adequate rehabilitative treatment according to patients’ needs.

Keywords: occupational therapy, social function, schizophrenia, visual perception

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Authors: Renata Gerhardt, Detlev Belder

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Raman spectroscopy has attracted much attention as a structurally descriptive and label-free detection method. It is particularly suited for chemical analysis given as it is non-destructive and molecules can be identified via the fingerprint region of the spectra. In this work possibilities are investigated how to integrate Raman spectroscopy as a detection method for chip-based chromatography, making use of a droplet interface. A demanding task in lab-on-a-chip applications is the specific and sensitive detection of low concentrated analytes in small volumes. Fluorescence detection is frequently utilized but restricted to fluorescent molecules. Furthermore, no structural information is provided. Another often applied technique is mass spectrometry which enables the identification of molecules based on their mass to charge ratio. Additionally, the obtained fragmentation pattern gives insight into the chemical structure. However, it is only applicable as an end-of-the-line detection because analytes are destroyed during measurements. In contrast to mass spectrometry, Raman spectroscopy can be applied on-chip and substances can be processed further downstream after detection. A major drawback of Raman spectroscopy is the inherent weakness of the Raman signal, which is due to the small cross-sections associated with the scattering process. Enhancement techniques, such as surface enhanced Raman spectroscopy (SERS), are employed to overcome the poor sensitivity even allowing detection on a single molecule level. In SERS measurements, Raman signal intensity is improved by several orders of magnitude if the analyte is in close proximity to nanostructured metal surfaces or nanoparticles. The main gain of lab-on-a-chip technology is the building block-like ability to seamlessly integrate different functionalities, such as synthesis, separation, derivatization and detection on a single device. We intend to utilize this powerful toolbox to realize Raman detection in chip-based chromatography. By interfacing on-chip separations with a droplet generator, the separated analytes are encapsulated into numerous discrete containers. These droplets can then be injected with a silver nanoparticle solution and investigated via Raman spectroscopy. Droplet microfluidics is a sub-discipline of microfluidics which instead of a continuous flow operates with the segmented flow. Segmented flow is created by merging two immiscible phases (usually an aqueous phase and oil) thus forming small discrete volumes of one phase in the carrier phase. The study surveys different chip designs to realize coupling of chip-based chromatography with droplet microfluidics. With regards to maintaining a sufficient flow rate for chromatographic separation and ensuring stable eluent flow over the column different flow rates of eluent and oil phase are tested. Furthermore, the detection of analytes in droplets with surface enhanced Raman spectroscopy is examined. The compartmentalization of separated compounds preserves the analytical resolution since the continuous phase restricts dispersion between the droplets. The droplets are ideal vessels for the insertion of silver colloids thus making use of the surface enhancement effect and improving the sensitivity of the detection. The long-term goal of this work is the first realization of coupling chip based chromatography with droplets microfluidics to employ surface enhanced Raman spectroscopy as means of detection.

Keywords: chip-based separation, chip LC, droplets, Raman spectroscopy, SERS

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Authors: Prajna Paramita Naik, Sujit Kumar Bhutia

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Background: Regardless of the development multimodal treatment strategies, oral squamous cell carcinoma (OSCC) is often associated with a high rate of recurrence, metastasis and chemo- and radio- resistance. The present study inspected the relevance of CD44, ABCB1 and ADAM17 expression as a putative stem cell compartment in oral squamous cell carcinoma (OSCC) and deciphered the role of autophagy in regulating the expression of aforementioned proteins, stemness and chemoresistance. Methods: A retrospective analysis of CD44, ABCB1 and ADAM17 expression with respect to the various clinicopathological factors of sixty OSCC patients were determined via immunohistochemistry. The correlation among CD44, ABCB1 and ADAM17 expression was established. Sphere formation assay, flow cytometry and fluorescence microscopy were conducted to elucidate the stemness and chemoresistance nature of established cisplatin-resistant oral cancer cells (FaDu). The pattern of expression of CD44, ABCB1 and ADAM17 in parental (FaDu-P) and resistant FaDu cells (FaDu-CDDP-R) were investigated through fluorescence microscopy. Western blot analysis of autophagy marker proteins was performed to compare the status of autophagy in parental and resistant FaDu cell. To investigate the role of autophagy in chemoresistance and stemness, sphere formation assay, immunofluorescence and Western blot analysis was performed post transfection with siATG14 and the level of expression of autophagic proteins, mitochondrial protein and stemness-associated proteins were analyzed. The statistical analysis was performed by GraphPad Prism 4.0 software. p-value was defined as follows: not significant (n.s.): p > 0.05;*: p ≤ 0.05; **: p ≤ 0.01; ***: p ≤ 0.001; ****: p ≤ 0.0001 were considered statistically significant. Results: In OSCC, high CD44, ABCB1 and ADAM17 expression were significantly correlated with higher tumor grades and poor differentiation. However, the expression of these proteins was not related to the age and sex of OSCC patients. Moreover, the expression of CD44, ABCB1 and ADAM17 were positively correlated with each other. In vitro and OSCC tissue double labeling experiment data showed that CD44+ cells were highly associated with ABCB1 and ADAM17 expression. Further, FaDu-CDDP-R cells showed higher sphere forming capacity along with increased fraction of the CD44+ population and β-catenin expression FaDu-CDDP-R cells also showed accelerated expression of CD44, ABCB1 and ADAM17. A comparatively higher autophagic flux was observed in FaDu-CDDP-R against FaDu-P cells. The expression of mitochondrial proteins was noticeably reduced in resistant cells as compared to parental cells indicating the occurrence of autophagy-mediated mitochondrial degradation in oral cancer. Moreover, inhibition of autophagy was coupled with the decreased formation of orospheres suggesting autophagy-mediated stemness in oral cancer. Blockade of autophagy was also found to induce the restoration of mitochondrial proteins in FaDu-CDDP-R cells indicating the involvement of mitophagy in chemoresistance. Furthermore, a reduced expression of CD44, ABCB1 and ADAM17 was also observed in ATG14 deficient cells FaDu-P and FaDu-CDDP-R cells. Conclusion: The CD44+ ⁄ABCB1+ ⁄ADAM17+ expression in OSCC might be associated with chemoresistance and a putative CSC compartment. Further, the present study highlights the contribution of mitophagy in chemoresistance and confirms the potential involvement of autophagic regulation in acquisition of stem-like characteristics in OSCC.

Keywords: ABCB1, ADAM17, autophagy, CD44, chemoresistance, mitophagy, OSCC, stemness

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Authors: Mehmet Salih Bayraktutan, Emre Tokmak

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Great Ararat Volcano is the highest peak in South Caucasus Volcanic Plateau. Uplifted by Quaternary basaltic pyroclastic and lava flows. Numerous volcanic cones formed along with the tensional fractures under N-S compressional geodynamic framework. Basaltic flows have fresh surface morphology give ages of 650-680 K years. Hyperstene andesites constitute a major mass of Greater Ararat gives ages of 450-490 K years. During the early eruption period, predominately pyroclastics, cinder, lapilly-ash volcanic bombs were extruded. Third-period eruptions dominantly basaltic lava flows. Andesitic domes aligned along with the NW-SE striking fractures. Hyalo basalt and hornblende basaltic lavas are the latest lava eruptions. Hyalo-basaltic eruptions occurred via parasitic cones distributed far from the center. Parasitic cones are most common at the foot of Mount covered by recent NW flowing basaltic lava. Some of the cones are distributed on a circular pattern. One of the most hazardous disasters recorded in Eastern Turkey was July 1840 Cehennem Canyon Flood. Volcanic activities seismically triggered resulted in melting of glacier cap, mixed with ash and pyroclastics, flowed down along the Valley. Mud rich Slush urged catastrophically northwards, crossed Ars River and damned Surmeli Basin, forming reservoir behind. Ararat volcanoes are located on NW-SE striking Agri Fault Zone. Right lateral extensional faults, along which a series of andesitic domes formed. Great Ararat, in general strato-type volcano. This huge structure, developed in two main parts with different topographic and morphological features. The large lower base covers a widespread area composed of predominantly pyroclastics, ignimbrites, aglomerates, thick pumice, perlite deposits. Approximately 1/3 of the Crest by height formed of this basement. And 2/3 of the upper part with a conic- shape composed of basaltic lava flows. The active tectonic structure consists of three different patterns. The first network is radially distributed fractures formed during the last stage of lava eruptions. The second group of active faults striking in NW direction, and continue in N30W strike, formes Igdir Fault Zone. The third set of faults, dipping in the northwest with 75-80 degrees, strikes NE- SW across the whole Mount, slicing Great Ararat into four segments. In the upper stage of Cehennem Canyon, this set cutting volcanic layers caused numerous Waterfalls, Rock Avalanches, Mud Flows along the canyon, threatens the Village of Yanidogan, at the apex of flood deposits. Great Ararat Region has high seismo-tectonic risk and by occurrence frequency and magnitude, which caused in history caused heavy disasters, at villages surrounding the Ararat Basement.

Keywords: Eastern Turkey, geohazard, great ararat volcano, seismo-tectonic features

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Authors: Zoi Konsoula

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Vegetable oils, which are rich in polyunsaturated fatty acids, are susceptible to oxidative deterioration. The lipid oxidation of oils results in the production of rancid odors and unpleasant flavors as well as the reduction of their nutritional quality and safety. Traditionally, synthetic antioxidants are employed for their retardation or prevention of oxidative deterioration of oils. However, these compounds are suspected to pose health hazards. Consequently, recently there has been a growing interest in the use of natural antioxidants of plant origin for improving the oxidative stability of vegetable oils. The genus Salvia (sage) is well known for its antioxidant activity. In the Cypriot flora Salvia fruticosa is the most distributed indigenous Salvia species. In the present study, extracts were prepared from S. fruticosa aerial parts using various solvents and their antioxidant activity was evaluated by the 1,1-diphenyl-2-picrylhydrazine (DPPH) radical scavenging and Ferric Reducing Antioxidant Power (FRAP) method. Moreover, the antioxidant efficacy of all extracts was assessed using corn oil as the oxidation substrate, which was subjected to accelerated aging (60 °C, 30 days). The progress of lipid oxidation was monitored by the determination of the peroxide, p-aniside, conjugated dienes and trienes value according to the official AOCS methods. Synthetic antioxidants (butylated hydroxytoluene-BHT and butylated hydroxyanisole-BHA) were employed at their legal limit (200 ppm) as reference. Finally, the total phenolic (TPC) and flavonoid content (TFC) of the prepared extracts was measured by the Folin-Ciocalteu and aluminum-flavonoid complex method, respectively. The results of the present study revealed that although all sage extracts prepared from S. fruticosa exhibited antioxidant activity, the highest antioxidant capacity was recorded in the methanolic extract, followed by the non-toxic, food grade ethanol. Furthermore, a positive correlation between the antioxidant potency and the TPC of extracts was observed in all cases. Interestingly, sage extracts prevented lipid oxidation in corn oil at all concentrations tested, however, the magnitude of stabilization was dose dependent. More specifically, results from the different oxidation parameters were in agreement with each other and indicated that the protection offered by the various extracts depended on their TPC. Among the extracts, the methanolic extract was more potent in inhibiting oxidative deterioration. Finally, both methanolic and ethanolic sage extracts at a concentration of 1000 ppm exerted a stabilizing effect comparable to that of the reference synthetic antioxidants. Based on the results of the present study, sage extracts could be used for minimizing or preventing lipid oxidation in oils and, thus, prolonging their shelf-life. In particular, given that the use of dietary alcohol, such as ethanol, is preferable than methanol in food applications, the ethanolic extract prepared from S. fruticosa could be used as an alternative natural antioxidant.

Keywords: antioxidant activity, corn oil, oxidative deterioration, sage

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Authors: N. Demertzis, J. L. Bowen

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Sepsis is a complex and rapidly evolving condition, resulting from uncontrolled prolonged activation of host immune system due to pathogenic insult. The aim of this study is the development of a multiplex electrochemical sensing platform, capable of detecting both pathogen associated and host immune markers to enable the rapid and definitive diagnosis of sepsis. A combination of aptamers and molecular imprinting approaches have been employed to generate sensing systems for lipopolysaccharide (LPS), c-reactive protein (CRP) and procalcitonin (PCT). Gold working electrodes were mechanically polished and electrochemically cleaned with 0.1 M sulphuric acid using cyclic voltammetry (CV). Following activation, a self-assembled monolayer (SAM) was generated, by incubating the electrodes with a thiolated anti-LPS aptamer / dithiodibutiric acid (DTBA) mixture (1:20). 3-aminophenylboronic acid (3-APBA) in combination with the anti-LPS aptamer was used for the development of the hybrid molecularly imprinted sensor (apta-MIP). Aptasensors, targeting PCT and CRP were also fabricated, following the same approach as in the case of LPS, with mercaptohexanol (MCH) replacing DTBA. In the case of the CRP aptasensor, the SAM was formed following incubation of a 1:1 aptamer: MCH mixture. However, in the case of PCT, the SAM was formed with the aptamer itself, with subsequent backfilling with 1 μM MCH. The binding performance of all systems has been evaluated using electrochemical impedance spectroscopy. The apta-MIP’s polymer thickness is controlled by varying the number of electropolymerisation cycles. In the ideal number of polymerisation cycles, the polymer must cover the electrode surface and create a binding pocket around LPS and its aptamer binding site. Less polymerisation cycles will create a hybrid system which resembles an aptasensor, while more cycles will be able to cover the complex and demonstrate a bulk polymer-like behaviour. Both aptasensor and apta-MIP were challenged with LPS and compared to conventional imprinted (absence of aptamer from the binding site, polymer formed in presence of LPS) and non-imprinted polymers (NIPS, absence of LPS whilst hybrid polymer is formed). A stable LPS aptasensor, capable of detecting down to 5 pg/ml of LPS was generated. The apparent Kd of the system was estimated at 17 pM, with a Bmax of approximately 50 pM. The aptasensor demonstrated high specificity to LPS. The apta-MIP demonstrated superior recognition properties with a limit of detection of 1 fg/ml and a Bmax of 100 pg/ml. The CRP and PCT aptasensors were both able to detect down to 5 pg/ml. Whilst full binding performance is currently being evaluated, there is none of the sensors demonstrate cross-reactivity towards LPS, CRP or PCT. In conclusion, stable aptasensors capable of detecting LPS, PCT and CRP at low concentrations have been generated. The realisation of a multiplex panel such as described herein, will effectively contribute to the rapid, personalised diagnosis of sepsis.

Keywords: aptamer, electrochemical impedance spectroscopy, molecularly imprinted polymers, sepsis

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Authors: Abiola O. Temitayo-Oboh, Olugbenga L. Abodunrin, Wasiu O. Adebimpe, Micheal C. Asuzu

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Introduction: Many women who are sexually active would prefer to avoid becoming pregnant but are not using any method of contraception. These women are considered to have an unmet need for contraception. In an ideal situation, all women who want to space or limit their births and are exposed to the risk of conception would use some kind of conception; in practice, however, some women fail to use contraception which put them at risk of having mistimed or unwanted births, induced abortion, or maternal death. This study, therefore, aimed to assess the determinants of unmet need for contraception among currently married women in rural and urban communities of Osun State, South-West Nigeria. Methods: This was an analytical cross-sectional comparative study, which was carried out among currently married women. Three hundred and twenty respondents each were selected for the rural and urban groups from four Local Government Areas using multi-stage sampling technique. Data were collected using a pre-tested semi-structured interviewer-administered questionnaire and focus group discussion (FGD) guide; data analysis was done with Statistical Package for Social Sciences (SPSS) version 17.0 and detailed content analysis method respectively. Statistical analysis of the difference between proportions was done by the use of the Chi-square test and T-test was used to compare the means of the continuous variables. The study also utilized descriptive, bivariate and multivariate analytical techniques to examine the effect of some variables on unmet need. Level of statistical significance was set at p-value < 0.05 for all values. Results: Two hundred and ninety-six (92.5%) of the rural and 306 (95.6%) of the urban study population had heard of contraception, 365 (57.0 %) of the total respondents had good knowledge [162 (50.6 %) for rural respondents and 203 (63.4 %) for urban respondents]. This difference was statistically significant (p < 0.001). Five hundred and twenty-one (81.4%) respondents had a positive attitude towards contraception [243 (75.9%) in the rural and 278 (86.9%) in the urban area], and the difference was also statistically significant (p < 0.001). Only 47 (14.7%) and 59 (18.4%) of rural and urban women were current contraceptive users respectively. The total unmet need for contraception among rural women was 138 (43.1%) of which 82 (25.6%) was for spacing and 56 (17.5%), for limiting. While the total unmet need for contraception among urban women was 145 (45.3%) of which 96 (30.0%) was for spacing and 49 (15.3%) for limiting. Number of living children, knowledge of contraceptive methods, discussion with health workers about family planning, couples discussion about family planning and availability of family planning services were found to be predictors of women’s unmet need for contraception (p < 0.05). Conclusion: It is, therefore, recommended that there is need to intensify reproductive health education in bridging the knowledge gap, improving attitude and modifying practices regarding use of contraception in Nigeria. Hence, this will help to enhance the utilization of family planning services among Nigerian women.

Keywords: contraception, married women, Nigeria, rural, urban, unmet need

Procedia PDF Downloads 178

Authors: Beverly Black

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Teen dating violence (TDV) is a significant public health problem with severe negative impact on youths’ mental and physical health and well-being. Exacerbating the negative impact of TDV victimization is the fact that teens rarely report the violence. They are fearful to tell friends or family, especially parents. The family context is the first place where children learn about interpersonal relationships, and therefore, parental response of teens’ life experiences influences teens’ actions and development. This study examined youths’ perspectives on parental responses to TDV. Effective parental responses to TDV may increase the likelihood that youth will leave abusive relationships. Method. Eleven gender-separate focus groups were conducted with 27 females and 28 males, ages 12 to 17, to discuss parental responses to teen dating violence. Youth were recruited from a metropolitan community in the southwestern part of the United States. Focus groups questions asked the middle and high school youth how they would want their parents to respond to them if they approached them about various incidents of dating violence. All focus groups were transcribed. Using QSR-N10, two researchers’ analyzed data first using open and axial coding techniques to find overarching themes. Researchers triangulated the coded data to ensure accurate interpretations of the participants’ messages and used the scenario questions to structure the coded results. Results. Most youths suggested that parents should simply talk with them; they recognized the importance of communication. Teens wanted parents to ask questions, educate them about healthy relationships, share their personal experiences, and give teens advice (tell them to break up, limit contact with perpetrator, go to police). Younger youth expressed more willingness to listen to parental advice. Older youth wanted their parents to give them the opportunity to make their decisions. Many of the teens’ comments focused on the importance of parents protecting the teen, providing support and empathy for the teen, and especially refraining from overreacting (not yelling, not getting angry and staying calm). Implications. Parents need to know how to effectively respond to youth needing to leave unhealthy relationships. Demanding that their children end a relationship may not be a realistic approach to TDV. A parent’s ineffective response, when approached by an adolescent for assistance in TDV, may influence a youth to dismiss parents and other adults as viable options for seeking assistance. Parents and prevention educators can learn from hearing youths’ voices about effective responses to TDV.

Keywords: adolescents dating abuse, adolescent and parent communication, parental responses to teen dating violence, teen dating violence

Procedia PDF Downloads 258

Authors: Suliman Al-Fayoumi, Sherri Amberg, Huafeng Zhou, Jack W. Singer, James P. Dean

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Pacritinib is an oral kinase inhibitor with specificity for JAK2, FLT3, IRAK1, and CSF1R. In clinical studies, pacritinib was well tolerated with clinical activity in patients with myelofibrosis. The most frequent adverse events (AEs) observed with pacritinib are gastrointestinal (diarrhea, nausea, and vomiting; mostly grade 1-2 in severity) and typically resolve within 2 weeks. A human ADME mass balance study demonstrated that pacritinib is predominantly cleared via hepatic metabolism and biliary excretion (>85% of administered dose). The major hepatic metabolite identified, M1, is not thought to materially contribute to the pharmacological activity of pacritinib. Hepatic diseases are known to impair hepatic blood flow, drug-metabolizing enzymes, and biliary transport systems and may affect drug absorption, disposition, efficacy, and toxicity. This phase 1 study evaluated the pharmacokinetics (PK) and safety of pacritinib and the M1 metabolite in study subjects with mild, moderate, or severe hepatic impairment (HI) and matched healthy subjects with normal liver function to determine if pacritinib dosage adjustments are necessary for patients with varying degrees of hepatic insufficiency. Study participants (aged 18-85 y) were enrolled into 4 groups based on their degree of HI as defined by Child-Pugh Clinical Assessment Score: mild (n=8), moderate (n=8), severe (n=4), and healthy volunteers (n=8) matched for age, BMI, and sex. Individuals with concomitant renal dysfunction or progressive liver disease were excluded. A single 400 mg dose of pacritinib was administered to all participants. Blood samples were obtained for PK evaluation predose and at multiple time points postdose through 168 h. Key PK parameters evaluated included maximum plasma concentration (Cmax), time to Cmax (Tmax), area under the plasma concentration time curve (AUC) from hour zero to last measurable concentration (AUC0-t), AUC extrapolated to infinity (AUC0-∞), and apparent terminal elimination half-life (t1/2). Following treatment, pacritinib was quantifiable for all study participants at 1 h through 168 h postdose. Systemic pacritinib exposure was similar between healthy volunteers and individuals with mild HI. However, there was a significant difference between those with moderate and severe HI and healthy volunteers with respect to peak concentration (Cmax) and plasma exposure (AUC0-t, AUC0-∞). Mean Cmax decreased by 47% and 57% respectively in participants with moderate and severe HI vs matched healthy volunteers. Similarly, mean AUC0-t decreased by 36% and 45% and mean AUC0-∞ decreased by 46% and 48%, respectively in individuals with moderate and severe HI vs healthy volunteers. Mean t1/2 ranged from 51.5 to 74.9 h across all groups. The variability on exposure ranged from 17.8% to 51.8% across all groups. Systemic exposure of M1 was also significantly decreased in study participants with moderate or severe HI vs. healthy participants and individuals with mild HI. These changes were not significantly dissimilar from the inter-patient variability in these parameters observed in healthy volunteers. All AEs were grade 1-2 in severity. Diarrhea and headache were the only AEs reported in >1 participant (n=4 each). Based on these observations, it is unlikely that dosage adjustments would be warranted in patients with mild, moderate, or severe HI treated with pacritinib.

Keywords: pacritinib, myelofibrosis, hepatic impairment, pharmacokinetics

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