Search results for: negative phase

Authors: Michael Shandalov, Tzvi Templeman, Michael Schmidt, Itzhak Kelson, Eyal Yahel

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We present a new method to produce a model system for the study of radiation damage in non-radioactive materials. The method is based on homogeneously incorporating 228Th ions in PbS thin films using a small volume chemical bath deposition (CBD) technique. The common way to alloy metals with radioactive elements is by melting pure elements, which requires considerable amounts of radioactive material with its safety consequences such as high sample activity. Controlled doping of the thin films with (very) small amounts (100-200ppm) of radioactive elements such as thorium is expected to provide a unique path for studying radiation damage in materials due to decay processes without the need of sealed enclosure. As a first stage, we developed CBD process for controlled doping of PbS thin films (~100 nm thick) with the stable isotope (t1/2~106 years), 232Th. Next, we developed CBD process for controlled doping of PbS thin films with active 228Th isotope. This was achieved by altering deposition parameters such as temperature, pH, reagent concentrations and time. The 228Th-doped films were characterized using X-ray diffraction, which indicated a single phase material. Film morphology and thickness were determined using scanning electron microscopy (SEM). Energy dispersive spectroscopy (EDS) mapping in the analytical transmission electron microscope (A-TEM), X-ray photoelectron spectroscopy (XPS) depth profiles and autoradiography indicated that the Th ions were homogeneously distributed throughout the films, suggesting Pb substitution by Th ions in the crystal lattice. The properties of the PbS (228Th) film activity were investigated by using alpha-spectroscopy and gamma spectroscopy. The resulting films are applicable for isochronal annealing of resistivity measurements and currently under investigation. This work shows promise as a model system for the analysis of dilute defect systems in semiconductor thin films.

Keywords: thin films, doping, radiation damage, chemical bath deposition

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Authors: Maja Ruzic-Baf, Vedrana Keteles, Andrea Debeljuh

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Younger and younger children are now using a smartphone, a device which has become ‘a must have’ and the life of children would be almost ‘unthinkable’ without one. Devices are becoming lighter and lighter but offering an array of options and applications as well as the unavoidable access to the Internet, without which it would be almost unusable. Numerous features such as taking of photographs, listening to music, information search on the Internet, access to social networks, usage of some of the chatting and messaging services, are only some of the numerous features offered by ‘smart’ devices. They have replaced the alarm clock, home phone, camera, tablet and other devices. Their use and possession have become a part of the everyday image of young people. Apart from the positive aspects, the use of smartphones has also some downsides. For instance, free time was usually spent in nature, playing, doing sports or other activities enabling children an adequate psychophysiological growth and development. The greater usage of smartphones during classes to check statuses on social networks, message your friends, play online games, are just some of the possible negative aspects of their application. Considering that the age of the population using smartphones is decreasing and that smartphones are no longer ‘foreign’ to children of pre-school age (smartphones are used at home or in coffee shops or shopping centers while waiting for their parents, playing video games often inappropriate to their age), particular attention must be paid to a very sensitive group, the teenagers who almost never separate from their ‘pets’. This paper is divided into two sections, theoretical and empirical ones. The theoretical section gives an overview of the pros and cons of the usage of smartphones, while the empirical section presents the results of a research conducted in three elementary schools regarding the usage of smartphones and, specifically, their usage during classes, during breaks and to search information on the Internet, check status updates and 'likes’ on the Facebook social network.

Keywords: education, smartphone, social networks, teenagers

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Authors: Geraldine Landon, Enora Clero, Jean-Rene Jourdain

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In 2005, the Institut de Radioprotection et de Sûreté Nucléaire (IRSN, France) launched a research program named EPICE (acronym for 'Evaluation of Pathologies potentially Induced by CaEsium') to collect scientific information on non-cancer effects possibly induced by chronic exposures to low doses of ionizing radiation with the view of addressing a question raised by several French NGOs related to health consequences of the Chernobyl nuclear accident in children. The implementation of the program was preceded by a pilot phase to ensure that the project would be feasible and determine the conditions for implementing an epidemiological study on a population of several thousand children. The EPICE program focused on childhood cardiac arrhythmias started in May 2009 for 4 years, in partnership with the Russian Bryansk Diagnostic Center. The purpose of this cross-sectional study was to determine the prevalence of cardiac arrhythmias in the Bryansk oblast (depending on the contamination of the territory and the caesium-137 whole-body burden) and to assess whether caesium-137 was or not a factor associated with the onset of cardiac arrhythmias. To address these questions, a study bringing together 18 152 children aged 2 to 18 years was initiated; each child received three medical examinations (ECG, echocardiography, and caesium-137 whole-body activity measurement) and some of them were given with a 24-hour Holter monitoring and blood tests. The findings of the study, currently submitted to an international journal justifying that no results can be given at this step, allow us to answer clearly to the issue of radiation-induced childhood arrhythmia, a subject that has been debated for many years. Our results will be certainly helpful for health professionals responsible for the monitoring of population exposed to the releases from the Fukushima Dai-ichi nuclear power plant and also useful for future comparative study in children exposed to ionizing radiation in other contexts, such as cancer radiation therapies.

Keywords: Caesium-137, cardiac arrhythmia, Chernobyl, children

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Authors: Endang Purwati Rahayuningsih

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The aim of this study is Enteropathogenic Eschericia coli O157 (EPEC) is one of the pathogen that can cause inflamation and damage intestinal mucosa, which is leading diarrhea. Inflamation in the intestinal mucosa proved by the presence of secretory Immunoglobulin A (sIgA) on the feces. Isolate dadih is Pediococcus pentosaceus (P. pentosaceus) as a probiotic lactic acid bacteria (LAB) is very usefull to improve sIgA and intestinal mucosa. The objective, to determine the dose and duration administration of P. pentosaceus for bowel frequence, sIgA level and height of illeum villi in mice EPEC-induced diarrhea. Method, using Complete Randomized design studies in mice EPEC-induced diarrhea. Mice was classified into 2 factors. A factor (dose of probiotic) and B factor (duration of probiotic observation) consisted of 0 hour, 12 hours, 24 hours and 36 hours. A factor consisted of negative control, positive control (mice induced by EPEC) and 3 different dose experimental mice. The results were a very significant interaction between dose and duration administration of P. pentosaceus. Mean of the most frequent defecation of mice EPEC-induced was 55 graetly reduced into 12 ,after 24 hours administration P. pentosaceus dose 2 x 1010 cfu/g, Mean of sIgA level of mice induced EPEC was 1,60 μg/ml, very significant different (p<0,01). Mean of sIgA level after 24 administration P. pentosaceus dose 2 x 1010cfu/g was 2,65 μg/ml. Mean of height of illeum villi after induced EPEC 53,04 μm with very significant different after 24 hours administration P. pentosaceus dose 2 x 1010cfu/g (142,881μm). This study concluded that P. pentosaceus dose 2 x 1010cfu/g after 24 hours is very beneficial to reduced bowel frequence, increase sIgA level and improve the height illeum villi of mice EPEC-induced diarrhea.

Keywords: Pediococcus pentosaceus, sIgA, enteropathogenic Eschericia coli O157, diarrhea, illeum villi

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Authors: Amna Imtiaz

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Aims: To correlate serum ferritin with left ventricular function in beta thalassemia major patients with increased transfusion dependence and to find out whether echocardiography can be used to assess pre clinical cardiac disease in these patients. Methods: The cross sectional study was conducted at Department of Pathology, Shaheed Zulfiqar Ali Bhutto Medical University, Pakistan Institute of Medical Sciences, Islamabad. 60 patients of beta thalassemia major with increased transfusion dependence were enrolled in this study. Serum ferritin levels of all patients were measured by using indirect enzyme linked immunosorbent assay (ELISA). Echocardiography was performed on all patients by a consultant cardiologist by linking conventional echocardiography with tissue Doppler imaging. Ejection fraction and E/A ratio were measured in all patients to assess left ventricular systolic and diastolic function. Results: On the basis of serum ferritin level, patients were divided into three groups. Group I consisted of patients having serum ferritin level equal to or less than 2500 ng/ml. A total of 25 patients were placed in this group. Group II included patients having serum ferritin level between 2500 to 5000 ng/ml. A total of 22 patients were placed in this group. Group III included patients having serum ferritin level more than 5000 ng/ml. This group consisted of 13 patients. All patients having serum ferritin below 2500ng/ml had normal systolic function, and only 16% of the patients in this group had diastolic dysfunction as reflected by abnormal E/A ratio. In group II, 27% of the patients had systolic dysfunction reflected by subnormal ejection fraction while 40% of the patients had diastolic dysfunction. In group III, 62% of the patients had abnormal systolic and diastolic function. Pearson correlation was used to find a correlation between serum ferritin and left ventricular function. A strong negative correlation was found which is reflected by a p value of less than 0.05 which is significant. Chi square test is used to correlate serum ferritin with E/A ratio. P value came out to be less than 0.05 which is significant.

Keywords: beta thalassemia major, left ventricular function, serum ferritin, transfusion dependence

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Authors: P. Selyshchev

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Construction materials for nuclear facilities are operated under extreme thermal and radiation conditions. First of all, they are nuclear fuel, fuel assemblies, and reactor vessel. It places high demands on the control of their state, stability of their state, and their operating conditions. An irradiated material is a typical example of an open non-equilibrium system with nonlinear feedbacks between its elements. Fluxes of energy, matter and entropy maintain states which are far away from thermal equilibrium. The links that arise under irradiation are inherently nonlinear. They form the mechanisms of feed-backs that can lead to instability. Due to this instability the temperature of the sample, heat transfer, and the defect density can exceed the steady-state value in several times. This can lead to change of typical operation and an accident. Therefore, it is necessary to take into account the thermal instability to avoid the emergency situation. The point is that non-thermal energy can be accumulated in materials because irradiation produces defects (first of all these are vacancies and interstitial atoms), which are metastable. The stored energy is about energy of defect formation. Thus, an annealing of the defects is accompanied by releasing of non-thermal stored energy into thermal one. Temperature of the material grows. Increase of temperature results in acceleration of defect annealing. Density of the defects drops and temperature grows more and more quickly. The positive feed-back is formed and self-reinforcing annealing of radiation defects develops. To describe these phenomena a theoretical approach to thermal instability is developed via formalism of complex systems. We consider system of nonlinear differential equations for different components of microstructure and temperature. The qualitative analysis of this non-linear dynamical system is carried out. Conditions for development of instability have been obtained. Points of bifurcation have been found. Convenient way to represent obtained results is a set of phase portraits. It has been shown that different regimes of material state under irradiation can develop. Thus degradation of irradiated material can be limited by means of choice appropriate kind of evolution of materials under irradiation.

Keywords: irradiation, material, non-equilibrium state, nonlinear feed-back, thermal instability

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Authors: Anees Tahir

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Margin financing plays a significant role in Pakistan's stock market (PSX), offering investors the opportunity to maximize profits by borrowing funds from financiers to purchase marginable stocks. However, this financial practice raises several Shariah-related concerns. The study follows legal doctrinal research methodology. It explains and analyzes the law of margin financing prevailing in PSX and compares it with the principles of Shariah. It also examines and investigates the practices of margin financing from the perspective of Shariah. As part of the study, the researcher has conducted structured interviews with the Shariah advisors of the finance industry, academicians, market practitioners, and regulators. Thus, the study analyzes the findings of interviews. This article explores the legal framework and practice of margin financing in Pakistan from a Shariah perspective. The article investigates various issues relating to margin financing, including the fundamental concern of interest-based lending, which contravenes Islamic principles. It also highlights the problematic subject matter of margin financing, often involving non-Shariah compliant securities. Additionally, the article addresses the restriction on proprietary rights and the problematic element of speculation associated with margin financing. To provide a Shariah-compliant alternative, the Securities and Exchange Commission of Pakistan (SECP) introduced Murabahah Shares Financing (MSF) in 2019. However, the focus of the market is still on conventional margin financing. In the opinion of the researcher, the effective implementation of MSF is imperative because in the absence of such an alternative, the faith sensitive investor will remain deprived of a level playing field, and he is unable to get required financing opportunities through a halal and Shariah-compliant manner. This article argues that margin financing in its current form is incompatible with Shariah principles and should be discontinued. It is recommended that the SECP should gradually phase out the use of margin financing and increase reliance on MSF to provide faith-sensitive and committed investors with Shariah-compliant financing options.

Keywords: margin financing, marginable stocks, faith sensitive investor, Murabahah shares financing

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Authors: Aurélia Jandot

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With the oil and economic crises which began in the 1970’s, it has progressively appeared necessary to convince the French “general public“ that a use of new energy sources was essential. In this field, nuclear energy represented the future and concentrated lots of hopes. However, the discourse about nuclear energy has progressively seen negative arguments growing in the French media. The gradual changes in the perception of nuclear energy will be studied here through the arguments given in the main French weekly newsmagazines, which had a great impact on the readers, thus on the “general public“, from the 1970’s to the end of the 1980’s. Indeed, to understand better these changes will be taken into account the major international events, the reorientations of the French domestic policy, and the evolutions of the nuclear technology. As this represents a considerable amount of copies and thus of information, will be selected here the main articles which emphasize the “mental images“ aiming to direct the thought of the readers, and which have led the public awareness and acceptance to evolve. From the 1970’s to the end of the 1980’s, two dichotomous trends are in confrontation : one is promoting the perception of the nuclear energy, the other is discrediting it. Moreover, these two trends are organized in two axes. The first axis is about the engineerings evolutions, such as the main French media represent them, with its approximations, its exaggerations, its fictions sometimes. Is added the will to make accessible to the “general public“ some concepts which are quite difficult to understand for the largest number. The second axis rests on the way the major accidents of the period are approached, including those of Three Mile Island and Chernobyl. Thanks to these accidents and because of the international relations evolutions, the ecologist movements and their impacts have progressively grown, with evident consequences on the public perception of nuclear energy and on the way the successive governments can implement new power plants in France. Then, in both cases, over the period considered, the language has changed, as the perceptible objectives of the communication, allowing to discern the deepest intentions of the newsmagazines editing. This is all these changes that will be emphasized, over a period where the nuclear energy technology, to there a field for specialists, bearing mystery and secret, has become a social issue seemingly open to all.

Keywords: social issues, public acceptance, mediatization, discourse changes

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Authors: Jyoti Manandhar Shrestha, Saurab Raj Joshi, Maya Shrestha, Prashanna Shrestha, Kshitij Chaulagain

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Background: The widespread use of non-steroidal anti-inflammatory drugs has increased the incidence of ulcer and serious complications, such as perforation and bleeding. Although, the H2 receptor blockers and proton pump inhibitors decrease the acid secretion and promote healing of ulcer, their value in preventing relapse, recurrence, “acid rebound” after cessation of therapy and associated long term adverse effects limit their utility. So to minimize this, the herbal plant Aloe vera having anti-oxidant, anti-inflammatory, mucus secreting, cyto-protective and healing property is believed to cure the peptic ulcer. Objectives: To observe whether oral treatment with Aloe vera gel can prevent peptic ulcer. Indomethacin and ethanol were used to induce gastric ulcers. Thirty six albino rats of either sex were randomly allotted to six groups of six animals each. The negative control was pretreated with normal saline, the positive controls received ranitidine (20 mg/kg) and the test group received Aloe vera gel (300 mg/kg) orally for eight days. Then, after a 24 hour fast Indomethacin (20 mg/kg) or 80% ethanol (2ml) was administered orally to induce ulceration. At the end of the study, the rats were sacrificed, their stomachs opened, the ulcer index studied and tissues sent for histopathological examination. Results: It was observed that, in indomethacin treated group, the ulcer index in control group was 8.167 ± 1.72.In the Aloe vera pretreated animals, the ulcer index was 2.83 ± 1.72 and the standard ranitidine pretreated group ulcer index was 1.67 ± 1.36. In ethanol treated group, the ulcer index in control group was 7.5 ± 2.73. In the Aloe vera pretreated animals, the ulcer index was 2.67 ± 1.75 and the standard ranitidine pretreated group ulcer index was 1.33±1.21. Both ranitidine and Aloe vera gel significantly prevented stomach from gastric ulceration induced by indomethacin and ethanol. Conclusion: The results indicated that Aloe vera gel is effective against indomethacin and ethanol mediated gastric ulcer.

Keywords: Aloe vera gel, ethanol, indomethacin, peptic ulcer, ranitidine

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Authors: Emmanuel Nkemakolam Okwuduba, Fransica Chinelo Offiah

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The technique of teaching chemistry to students is one of the determining factors towards their achievement. Thus, the study investigated the relationship between classroom interaction patterns and students’ achievement in Chemistry. The purpose of this study was to identify patterns of interaction in an observed chemistry classroom, determine the amount of teacher talk, student talk and period of silence and to find out the relationship between them and the mean achievement scores of students. Five research questions and three hypotheses guided the study. The study was a correlational survey. The sample consisted of 450 (212males and 238 females) senior secondary one students and 12 (5males and 7 females) chemistry teachers drawn from 12 selected secondary schools in Awka Education Zone of Anambra state. In each of the 12 selected schools, an intact class was used. Science Interaction Category (SIC) and Chemistry Achievement Test (CAT) were developed, validated and used for data collection. Each teacher was observed three times and the interaction patterns coded using a coding sheet containing the Science Interaction Category. At the end of the observational period, the Chemistry Achievement Test (for collection of data on students’ achievement in chemistry) was administered on the students. Frequencies, percentage, mean, standard deviation and Pearson product moment correlation were used for data analysis. The result showed that the percentages of teacher talk, student talk and silence were 59.6%, 37.6% and 2.8% respectively. The Pearson correlation coefficient(r) for teacher talk, student talk and silence were -0.61, 0.76 and-0.18 respectively. The result showed negative and significant relationship between teacher talk and mean achievement scores of students; positive and significant relationship between student talk and mean achievement scores of students but there is no relationship between period of silence and mean achievement scores of students at 0.05 significant levels. The following recommendations were made based on the findings: teachers should establish high level of student talk through initiation and response as it promotes involvement and enhances achievement.

Keywords: academic achievement, chemistry, classroom, interactions patterns

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Authors: Abdul Matin, Muazzama Akhtar, Shahid Nisar, Saddaf Mazzar, Umer Rashid

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Antibiotic resistance is an increasing concern worldwide now a day. Neisseria gonorrhea and Staphylococcus aureus are known to cause major human sexually transmitted and respiratory diseases respectively. Nanotechnology is an emerging discipline and its application in various fields especially in medical sciences is gigantic. In the present study, we synthesized multi-walled carbon nanotubes (MWNTs) using acid oxidation method and solubilized MWNTs were with length predominantly >500 nm and diameters ranging from 40 to 50 nm. The locally synthesized MWNTs were used against gram positive and negative bacteria to determine their impact on bacterial growth. Clinical isolates of Neisseria gonorrhea (isolate: 4C-11) and Staphylococcus aureus (isolate: 38541) were obtained from local hospital and normally cultured in LB broth at 37°C. Both clinical strains can be obtained on request from University of Gujarat. Spectophometric assay was performed to determine the impact of MWNTs on bacterial growth in vitro. To determine the effect of MWTNs on test organisms, various concentration of MWNTs were used and recorded observation on various time intervals to understand the growth inhibition pattern. Our results demonstrated that MWNTs exhibited toxic effects to Staphylococcus aureus while showed very limited growth inhibition to Neisseria gonorrhea, which suggests the resistant potential of Neisseria against nanoparticles. Our results clearly demonstrate the gradual decrease in bacterial numbers with passage of time when compared with control. Maximum bacterial inhibition was observed at maximum concentration (50 µg/ml). Our future work will include further characterization and mode of action of our locally synthesized MWNTs. In conclusion, we investigated and reported for the first time the inhibitory potential of locally synthesized MWNTs on local clinical isolates of Staphylococcus aureus and Neisseria gonorrhea.

Keywords: antibacterial activity, multi walled carbon nanotubes, Neisseria gonorrhea, spectrophotometer assay, Staphylococcus aureus

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Authors: Lonna Mabandla, Godfrey Musvoto

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Transportation is a catalytic feature in cities. Transport and land use activity are interdependent and have a feedback loop between how land is developed and how transportation systems are designed and used. This recursive relationship between land use and transportation is reflected in how public transportation routes internal to the inner-city enhance accessibility, therefore creating spaces that are conducive to business activity, while the business activity also informs public transportation routes. It is for this reason that the focus of this research is on public transportation within inner-city areas where the dynamic is evident. Durban is the chosen case study where the dominating form of public transportation within the central business district (CBD) is minibus taxis. The paradox here is that minibus taxis still form part of the informal economy even though they are the leading form of public transportation in South Africa. There have been many attempts to formalise this industry to follow more regulatory practices, but minibus taxis are privately owned, therefore complicating any proposed intervention. The argument of this study is that the application of collaborative planning through a sustainable partnership between the public and private sectors will improve the social and environmental sustainability of public transportation. One of the major challenges that exist within such collaborative endeavors is power dynamics. As a result, a key focus of the study is on power relations. Practically, power relations should be observed over an extended period, specifically when the different stakeholders engage with each other, to reflect valid data. However, a lengthy data collection process was not possible to observe during the data collection phase of this research. Instead, interviews were conducted focusing on existing procedural planning practices between the inner-city minibus taxi association (South and North Beach Taxi Association), the eThekwini Transport Authority (ETA), and the eThekwini Town Planning Department. Conclusions and recommendations were then generated based on these data.

Keywords: collaborative planning, sustainability, public transport, minibus taxis

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Authors: Azad Hussain, Andrew Cobley

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The demand for lightweight parts with high mechanical strength(s) and integrity, in sectors such as the aerospace and automotive is ever increasing, motivated by the need for weight reduction in order to increase fuel efficiency with components usually manufactured using a high grade primary metal or alloy. For components manufactured using the squeeze casting process, this alloy is usually A356 aluminium (Al), it is one of the most versatile Al alloys; and is used extensively in castings for demanding environments. The A356 castings provide good strength to weight ratio making it an attractive option for components where strength has to be maintained, with the added advantage of weight reduction. In addition, the versatility in castabilitiy, weldability and corrosion resistance are other attributes that provide for the A356 cast alloy to be used in a large array of industrial applications. Conversely, it is rare to use remelted Al in these cases, due the nature of the applications of components in demanding environments, were material properties must be defined to meet certain specifications for example a known strength or ductility. However the use of remelted Al, especially primary grade Al such as A356, would offer significant cost and energy savings for manufacturers using primary alloys, provided that remelted aluminium can offer similar benefits in terms of material microstructure and mechanical properties. This study presents the results of the material microstructure and properties of 100% primary A356 Al and 100% remelt Al cast, manufactured via the direct squeeze cast method. The microstructures of the castings made from remelted A356 Al were then compared with the microstructures of primary A356 Al. The outcome of using remelting Al on the microstructure was examined via different analytical techniques, optical microscopy of polished and etched surfaces, and scanning electron microscopy. Microstructural analysis of the 100% remelted Al when compared with primary Al show similar α-Al phase, primary Al dendrites, particles and eutectic constituents. Mechanical testing of cast samples will elucidate further information as to the suitability of utilising 100% remelt for casting.

Keywords: A356, microstructure, remelt, squeeze casting

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Authors: Davaakhuu Vandannyam, Amarsaikhan Dashtseren, Oyungoo Badamdorj

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Background: Shift work and extended working hours are increasing in many industries and organization's in the world. Over a 24 hour period, the circadian clock regulates sleep/wake patterns, body temperature, hormone levels, digestion and many other functions. Depending on the time of day or night, the human body is programmed for periods of wakefulness and sleep, high and low body temperature, high and low digestive activity and so on. Shift work is highly prevalent in industrialized societies (>20%) but, when it includes night work, it has pronounced negative effects on sleep, subjective and physiological sleepiness, performance, accident risk, as well as on health outcomes such as cardiovascular disease and certain forms of cancer. Method: In this cross-sectional field study, 634 shift work and day work nurses from a plant were involved, with participation rate of 100% (634 nurses). The general health questionnaire (GHQ-28) and RLS, ESS, ISI, FSS were used to evaluate the level of insomnia, sleepiness, fatigue and restless legs syndrome, respectively. Results: As a result of research on some indicators of health risks caused from work shift, it was proven that prevalence of restless legs syndrome was at 5.5% and 25.9% are in risk of becoming sick, 42.3% are in fatigue, 3.5% in high stage of insomnia and 27.4% are sleepy on duty. Insomnia of nurses mainly affected from long-hour shift, dissatisfaction, workload, lose of focus and use of coffee. There is sleepiness lies in the workplace due to number of shifts, unsatisfactory performance and emergency calls between shifts. It has been determined that risk of sickness influenced by number of shifts in a month and long hour shift, dissatisfaction and use of coffee and divisions are causing restless legs syndrome. Conclusions: Among the nurses, it was found that the prevalence of insomnia is 31.6%, sleepiness 27.4%, fatigue 42.3%, restless legs syndrome 35% and stress 25.9%. These factors of shift work affecting health tend to go up as working hours increase and more common among shift work nurses.

Keywords: shiftwork, insomnia, sleepiness, restless

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Authors: Dalma Varga, Nora Hubayne H.

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Nowadays, among the measures taken to offset the consequences of climate change, water resources management is one of the key tools, which can include excess water management. As a result of climate change’s effects and as a result of the frequent inappropriate landuse, more and more areas are affected by the excess water inundation. Hungary is located in the deepest part of the Pannonian Basin, which is exposed to water damage – especially lowland areas that are endangered by floods or excess waters. The periodical presence of excess water creates specific habitats in a given area, which have ecological, functional, and aesthetic values. Excess water inundation affects approximately 74% of Hungary’s lowland areas, of which about 46% is also under nature protection (such as national parks, protected landscape areas, nature conservation areas, Natura 2000 sites, etc.). These data prove that areas exposed to excess water inundation – which are predominantly characterized by agricultural land uses – have an important ecological role. Other research works have confirmed the presence of numerous rare and endangered plant species in drainage canals, on grasslands exposed to excess water, and on special agricultural fields with mud vegetation. The goal of this research is to define and analyze ecosystem services of areas exposed to excess water inundation. In addition to this, it is also important to determine the quantified indicators of these areas’ natural and landscape values besides the presence of protected species and the naturalness of habitats, so all in all, to analyze the various nature protections related to excess water. As a result, a practice-orientated assessment method has been developed that provides the ecological water demand, assimilates to ecological and habitat aspects, contributes to adaptive excess water management, and last but not least, increases or maintains the share of the green infrastructure network. In this way, it also contributes to reduce and mitigate the negative effects of climate change.

Keywords: ecosystem services, landscape architecture, excess water management, green infrastructure planning

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Authors: Zahra Alqahtani

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The use of e-learning technologies is gaining momentum in all educational institutions of the world, including Saudi universities. In the e-learning context, there is a growing need and concern among Saudi universities to improve and enhance quality assurance for e-learning systems. Practicing quality assurance activities and applying quality standards in e-learning in Saudi universities is thought to reduce the negative viewpoints of some stakeholders and ensure stakeholders’ satisfaction and needs. As a contribution to improving the quality of e-learning method in Saudi universities, the main purpose of this study is to explore and investigate strategies for the development of quality assurance in e-learning in one university in Saudi Arabia, which is considered a good reference university using the best and ongoing practices in e-learning systems among Saudi universities. In order to ensure the quality of its e-learning methods, Saudi university has adopted Quality Matters Standards as a controlling guide for the quality of its blended and full e-course electronic courses. Furthermore, quality assurance can be further improved if a variety of perspectives are taken into consideration from the comprehensive viewpoints of faculty members, administrative staff, and students.This qualitative research involved the use of different types of interviews, as well as documents that contain data related to e-learning methods in the Saudi university environment. This exploratory case study was undertaken, from the perspectives of various participants, to understand the phenomenon of quality assurance using an inductive technique.The results revealed six main supportive factors that assist in ensuring the quality of e-learning in the Saudi university environment. Essentially, these factors are institutional support, faculty member support, evaluation of faculty, quality of e-course design, technology support, and student support, which together have a remarkable positive effect on quality, forming intrinsic columns connected by bricks leading to quality e-learning. Quality Matters standards are considered to have a strong impact on improving faculty members' skills and on the development of high-quality blended and full e-courses.

Keywords: E-learning, quality assurance, quality matters standards, KKU-supportive factors

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Authors: Etleva Hamzaraj, Eva Kica, Anila Paparisto, Pranvera Lazo

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Worldwide demographic developments of recent decades have been associated with negative environmental consequences. For this reason, there is a growing interest in assessing the state of natural ecosystems or assessing human impact on them. In this respect, this study aims to evaluate the change in water quality of the Mat River for a period of about ten years to highlight human impact. In one year, period of study, several biological and environmental parameters are determined to evaluate river water quality, and the data collected are compared with those of a similar study in 2007. Samples are collected every month in five stations evenly distributed along the river. Total coliform bacteria, the number of heterotrophic bacteria in water, and benthic macroinvertebrates are used as biological parameters of water quality. The most probable number index is used for evaluation of total coliform bacteria in water, while the number of heterotrophic bacteria is determined by counting colonies on plates with Plate Count Agar, cultivated with 0.1 ml sample after series dilutions. Benthic macroinvertebrates are analyzed by the number of individuals per taxa, the value of biotic index, EPT Richness Index value and tolerance value. Environmental parameters like pH, temperature, and electrical conductivity are measured onsite. As expected, the bacterial load was higher near urban areas, and the pollution increased with the course of the river. The maximum concentration of fecal coliforms was 1100 MPN/100 ml in summer and near the most urbanized area of the river. The data collected during this study show that after about ten years, there is a change in water quality of Mat River. According to a similar study carried out in 2007, the water of Mat River was of ‘excellent’ quality. But, according to this study, the water was classified as of ‘excellent’ quality only in one sampling site, near river source, while in all other stations was of ‘good’ quality. This result is based on biological and environmental parameters measured. The human impact on the quality of water of Mat River is more than evident.

Keywords: water quality, coliform bacteria, MPN index, benthic macroinvertebrates, biotic index

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Authors: Wisam Ismail, Brendan Wooler, Penelope McManus

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Introduction: The public perception of implants has been damaged in the wake of recent negative publicity and increasingly we are finding patients wanting to avoid them. Planned lipo-modelling to enhance the volume of a Latissimus dorsi flap is a viable alternative to silicone implants and maintains a Totally Autologous Technique (TAT). Here we demonstrate that when compared to an Implant Assisted Technique (IAT), a TAT offers patients many benefits that offset the requirement of more operations initially, with reduced short and long term complications, reduced symmetrisation surgery and reduced revision rates. Methods. Data was collected prospectively over 7 years. The minimum follows up was 3 years. The technique was generally standardized in the hand of one surgeon. All flaps were extended LD flaps (ELD). Lipo-modelling was performed using standard techniques. Outcome measures were unplanned secondary procedures, complication rates, and contralateral symmetrisation surgery rates. Key Results Were: Lower complication rates in the TAT group (18.5% vs. 33.3%), despite higher radiotherapy rates (TAT=49%, IAT=36.8%), TAT was associated with lower subsequent symmetrisation rates (30.6% vs. 50.9%), IAT had a relative risk of 3.1 for subsequent unplanned procedure, Autologous patients required an average of 1.76 sessions of lipo-modelling, Conclusions: Using lipo-modelling to enable totally autologous LD reconstruction offers significant advantages over an implant assisted technique. We have shown a lower subsequent unplanned procedure rate, lower revision surgery, and less contralateral symmetrisation surgery. We anticipate that a TAT will be supported by patient satisfaction surveys and long-term patient-reported cosmetic outcome data and intended to study this.

Keywords: breast, Latissimus dorsi, lipomodelling, reconstruction

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Authors: Cóndor C. José, Rodrigues E. Camila, Noronha L. Irene, Dos Santos Fernando, Irigoyen M. Claudia, Andrade Lúcia

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Sepsis induces alterations in hemodynamics and autonomic nervous system (ASN). The autonomic activity can be calculated by measuring heart rate variability (HRV) that represents the complex interplay between ASN and cardiac pacemaker cells. Wharton’s jelly mesenchymal stem cells (WJ-MSCs) are known to express genes and secreted factors involved in neuroprotective and immunological effects, also to improve the survival in experimental septic animals. We hypothesized, that WJ-MSCs present an important role in the autonomic activity and in the hemodynamic effects in a cecal ligation and puncture (CLP) model of sepsis. Methods: We used flow cytometry to evaluate WJ-MSCs phenotypes. We divided Wistar rats into groups: sham (shamoperated); CLP; and CLP+MSC (106 WJ-MSCs, i.p., 6 h after CLP). At 24 h post-CLP, we recorded the systolic arterial pressure (SAP) and heart rate (HR) over 20 min. The spectral analysis of HR and SAP; also the spontaneous baroreflex sensitivity (measure by bradycardic and tachycardic responses) were evaluated after recording. The one-way ANOVA and the post hoc Student– Newman– Keuls tests (P< 0.05) were used to data comparison Results: WJ-MSCs were negative for CD3, CD34, CD45 and HLA-DR, whereas they were positive for CD73, CD90 and CD105. The CLP group showed a reduction in variance of overall variability and in high-frequency power of HR (heart parasympathetic activity); furthermore, there is a low-frequency reduction of SAP (blood vessels sympathetic activity). The treatment with WJ-MSCs improved the autonomic activity by increasing the high and lowfrequency power; and restore the baroreflex sensitive. Conclusions: WJ-MSCs attenuate the impairment of autonomic control of the heart and vessels and might therefore play a protective role in sepsis. (Supported by FAPESP).

Keywords: baroreflex response, heart rate variability, sepsis, wharton’s jelly-derived mesenchymal stem cells

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Authors: Avani Maniar, Shivani Mehta

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Population aging is one of the most challenging issues of the twenty-first century, facing both developed and developing countries worldwide. In the developed world, there has already been a substantial amount of research on aging and work to help understand the capacity and potential of older people. They attract ever ones attention. Their existence in human society gives rise to variety of responses, reactions and apprehensions, because it connotes on greater part, to some kind of compulsion or willingness that prompt elderly to decide to work after retirement. Work due to social attention and assurance for security both economical and social. In this age, elderly aspire for psychological security with due attention. But the fact remains that despite age related limitations good number of persons in their age of sixty and beyond were hunting for work that would support them and get them some kind of support and in it turns helps them to remain physically and mentally active. Based on the existing diversities in the ageing process, it may be stated that there is a need to pay greater attention to the increasing awareness on the ageing issues and its socio-economic effects and to promote the development of policies and programmes for dealing with an ageing society. Addressing the needs, wants, and well-being of elderly people is essential for maintaining a healthy productive workforce in an aging society. This paper will draw on the results of the study about reasons of elderly working post retirement, problems faced by them and about the future of retirement to ask how widespread negative attitudes and stereotypes among employers are and whether these attitudes influence behavior towards older employees. The aim of research is not only to point out certain stereotypes concerning the elderly labour force, but also to stress that unless preconditions for overcoming these stereotypes are created and employment opportunities are given to this segment of the labour force, full employment as an ultimate goal of global economic policy cannot be achieved.

Keywords: employers, India, inequality, problems, reasons of working, silver workers

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Authors: Nino KItoshvili

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The family is an integral part of society, which plays a major role in the socialization and the formation of a person as a full member of society. The marital conflict even harms family members and finds a different effect on each member of the family, especially on children. There is a significant difference in the behavior of adolescents in conflict and non-conflict families. In times of marital conflict, adolescent psycho-social well-being is significantly dependent on socio-cultural mediating variables such as; Family income; Parenting style; The functioning of the family, and the existence of psycho-social support. In a family with low economic performance, low psychosocial harassment, family dysfunction, and bad parenting style, marital conflict significantly increases the risk of deteriorating adolescent psycho-social well-being. At this time, to support the well-being of the child, a special role is played by improving the marital relationship, which must be supported by state and community services. There are very few family studies in this field in Georgia, the therapeutic direction of the family is at an early stage, and there are no family-supporting psycho-social programs. This increases the chances of adolescent psycho-social well-being deteriorating amd socialization problems. The study will examine the mediating variables of marital conflict and adolescent psycho-social well-being and will attempt to determine their mediating and moderating role. Research suggests that an increase in the rate of marital conflict is associated with a decrease in child well-being. The well-being of children in conflict families is lower than that of children in non-conflict families and depends on the variables of mediating variables. Quantitative research will be conducted to study this phenomenon through a questionnaire developed and standardized in the research process. The study will be attended by families living in Georgia - spouses (married) and their adolescent children. By analyzing the data obtained from the research, we will be able to determine in which cases the intensity of the relationship between the marital conflict and the well-being of the adolescent increases or decreases; To conclude the mediating and moderating role of mediating variables and also to make relevant recommendations to reduce the negative impact on the psycho-social well-being of a child of marital conflict.

Keywords: adolescent, mediation, moderation, conflict, couple, well-being

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Authors: M. A. Ojo, E. O. Ogbole, A. O. Ojo

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This study analysed improved household solid waste management system in Minna metropolis, Niger state. Multi-staged sampling technique was used to administer 155 questionnaires to respondents, where Minna was divided into two income groups A and B based on the quality of the respondent’s houses. Primary data was collected with the aid of structured questionnaires and analysed using descriptive statistics to obtain results for the socioeconomic characteristics of respondents, types of waste generated and methods of disposing solid waste, the level of awareness and reliability of waste disposal methods as well as the willingness of households to pay for solid waste management in the area. The results revealed that majority of the household heads in the study area were male, 94.20% of the household heads fell between the ages of 21 and 50 and also that 96.80% of them had one form of formal education or the other. The results also revealed that 47.10% and 43.20% of the households generated food wastes and polymers respectively as a major constituent of waste disposed. The results of this study went further to reveal that 81.90% of the household heads were aware of the use of collection cans as a method of waste disposal while only 32.90% of them considered the method highly reliable. Multiple regression was used to determine the factors affecting the willingness of households to pay for waste disposal in the study area. The results showed that 76.10% of the respondents were willing to pay for solid waste management which indicates that households in Minna are concerned and willing to cater for their immediate environment. The multiple regression results revealed that age, income, environmental awareness and household expenditure have a positive and statistically significant relationship with the willingness of households to pay for waste disposal in the area while household size has a negative and statistically significant relationship with households’ willingness to pay. Based on these findings, it was recommended that more waste management services be made readily available to residents of Minna, waste collection service should be privatised to increase their effectiveness through increased competition and also that community participatory approach be used to create more environmental awareness amongst residents.

Keywords: household, solid waste, management, WTP

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Authors: Kim Kennedy, Daren Gibson, Stephanie Flukes, Chandra Diwakarla, Lisa Spalding, Leanne Pilkington, Andrew Redfern

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Introduction: It is well known that patients with Head and Neck Cancer (HNC) are at increased risk of subsequent head and neck cancers due to various aetiologies. Aim: We sought to determine the factors contributing to an increased risk of subsequent HNC primaries, and also to evaluate whether Aboriginal patients are at increased risk. Methods: We performed a retrospective cohort analysis of 320 HNC patients from a single centre in Western Australia, identifying 80 Aboriginal patients and 240 non-Aboriginal patients matched on a 1:3 ratio by site, histology, rurality, and age. We collected patient data including smoking and alcohol consumption, tumour and treatment data, and data on subsequent HNC primaries. Results: A subsequent HNC primary was seen in 37 patients (11.6%) overall. There was no significant difference in the rate of second primary HNCs between Aboriginal patients (12.5%) and nonAboriginal patients (11.2%) (p=0.408). Subsequent HNCs, were strongly associated with smoking and alcohol consumption however, with 95% of patients with a second primary being ever-smokers, and 54% of patients with a second primary having a history of excessive alcohol consumption. In the 37 patients with multiple HNC primaries, there were a total of 57 HNCs, with 29 patients having two primaries, six patients having 3 HNC primaries, one patient with four, and one with six. 54 out of the 57 cancers were in ever smokers (94.7%). There were only two multiple HNC primaries in a never smoker, non-drinker, and these cases were of unknown etiology with HPV/p16 status unknown in both cases. In the whole study population, there were 32 HPV-positive HNCs, and 67 p16-positive HNCs, with only two 2 nd HNCs in a p16-positive case, giving a rate of 3% in the p16+ population, which is actually much lower than the rate of second primaries seen in the overall population (11.6%), and was highest in the p16-negative population (15.7%). This suggests that p16-positivity is not a strong risk factor for subsequent primaries, and in fact p16-negativity appeared to be associated with increased risk, however this data is limited by the large number of patients without documented p16 status (45.3% overall, 12% for oropharyngeal, and 59.6% for oral cavity primaries had unknown p16 status). Summary: Subsequent HNC primaries were strongly associated with smoking and alcohol excess. Second and later HNC primaries did not appear to occur at increased rates in Aboriginal patients compared with non-Aboriginal patients, and p16-positivity did not predict increased risk, however p16-negativity was associated with an increased risk of subsequent HNCs.

Keywords: head and neck cancer, multiple primaries, aboriginal, p16 status, smoking, alcohol

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Authors: Melek Göregenli, Pelin Karakuş

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This present study explored the acculturation strategies and urban related identity of Turk and Kurd internal migrants from different regions of Turkey who resettled in three big cities in the west. Besides we aimed at a comparative analysis of acculturation strategies and urban-related identity of voluntary and internally displaced Kurd migrants. Particularly we explored the role of migration type, satisfaction with migration decision, urban-related identity and several socio demographic variables as predictors of Kurds’ integration strategy preference. The sample consisted of 412 adult participants from Izmir (64 females, 86 males); Ankara (76 females, 75 males); and Istanbul (43 females, 64 males and four unreported). In terms of acculturation strategies, assimilation was found to be the most preferred acculturation attitude among Turks whereas separation was found to be most endorsed acculturation attitude among Kurds. The migrants in Izmir were found to prefer assimilation whereas the migrants in Ankara prefer separation. Concerning urban-related identity mean scores, Turks reported higher urban-related identity scores than Kurds. Furthermore the internal migrants in Izmir were found to score higher in urban-related identity than the migrants living in Istanbul and Ankara. The results of the regression analysis revealed that gender, length of residence and migration type were the significant predictors of integration preference of Kurds. Thus, whereas gender and migration type had significant negative associations; length of residence had positive significant associations with Kurds integration preference. Compared to female Kurds, male Kurds were found to be more integrated. Furthermore, voluntary Kurd migrants were more favour of integration than internally displaced Kurds. The findings supported the significant associations between acculturation strategies and urban-related identity with either group.

Keywords: acculturation, forced migration, internal displacement, internal migration, Turkey, urban-related identity

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Authors: Ali Bayram, Remzi Yiğiter

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Objective: Alzheimer's disease (AD), the most common cause of dementia, is a progressive neurodegenerative disease. At present, diagnosis of AD is rather late in the disease. Therefore, we attempted to find peripheral biomarkers for the early diagnosis of AD. Herein, we conducted a study to investigate the unc-51 like autophagy activating kinase-1 (ULK1) mRNA expression levels in human peripheral blood mononuclear cells from patients with Alzheimer's disease. Method: To determine whether ULK1 gene expression are altered in AD patients, we measured their gene expression in human peripheral blood cell in 50 patients with AD and 50 age and gender matched healthy controls by quantitative real-time PCR technique. Results: We found that both ULK1 gene expression in peripheral blood cell were significantly decreased in patients with AD as compared with controls (p <0.05). Lower levels of ULK1 gene expression were significantly associated with the increased risk for AD. Conclusions: Serine/threonine-protein kinase involved in autophagy in response to starvation. Acts upstream of phosphatidylinositol 3-kinase PIK3C3 to regulate the formation of autophagophores, the precursors of autophagosomes. Part of regulatory feedback loops in autophagy: acts both as a downstream effector and negative regulator of mammalian target of rapamycin complex 1 (mTORC1) via interaction with RPTOR. Activated via phosphorylation by AMPK and also acts as a regulator of AMPK by mediating phosphorylation of AMPK subunits PRKAA1, PRKAB2, and PRKAG1, leading to negatively regulate AMPK activity. May phosphorylate ATG13/KIAA0652 and RPTOR; however such data need additional evidences. Plays a role early in neuronal differentiation and is required for granule cell axon formation. Alzheimer is the most common neurodegenerative disease. Our results provide useful information that the ULK1 gene expression is decreased in the neurodegeneration and AD patients with, indicating their possible systemic involvement in AD.

Keywords: Alzheimer’s sisease, ULK1, mRNA expression, RT-PCR

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Authors: Touhami Tahenni

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Excessively wide cracks are harmful to the serviceability of reinforced concrete (RC) beams and may lead to durability problems in the longer term. They also reduce the rigidity of RC sections, rendering the tensile concrete ineffective structurally. To reduce the negative effects of cracks, steel fibers are added to concrete mixes in the same manner as aggregates. In the present work, steel fibers reinforced concrete (SFRC) beams, made of normal strength and high strength concretes, were tested in a four-point bending test using a digital image correlation technique. The beams had different volume fractions of fibres and different aspect ratios (fiber length/fiber diameter). The evaluation of flexural cracking widths was determined using Gom-Aramis software. The experimental crack widths were compared with theoretical values predicted by the technical document of Rilem TC 162-TDF. The model proposed in this document seems to be the only one that considers the efficiency of steel fibres in restraining the crack widths. However, the model of Rilem takes into account only the aspect ratio of steel fibres to predict the crack width of SFRC beams. It has been reported in several pieces of research that the contribution of steel fibres to the limitation of flexural cracking widths is based on three essential parameters namely, the volume fraction, the orientation and the aspect ratio of fibres. Referring to the literature on the flexural cracking behavior of SFRC beams and the experimental observations of the present work, a correction of the Rilem model by the introduction of these parameters in the formula is proposed. The crack widths predicted by the new empirical model were compared with the experimental results and assessed against other test data on SFRC beams taken from the literature. The modified Rilem model gives better results and is found more satisfactory in predicting the crack widths of fibres concrete.

Keywords: stee fibres, reinforced concrete, flexural cracking, tensile strength, crack width

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Authors: B. Laurita

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The importance of Water Harvesting (WH) as an effective mean to deal with water scarcity is universally recognized. The collection and storage of rainwater, floodwater or quick runoff and their conversion to productive uses can ensure water availability for domestic and agricultural use, enabling a lower exploitation of the aquifer, preventing erosion events and providing significant ecosystem services. At the same time, it has been proven that it can reduce the insurgence of water conflicts if supported by a cooperative process of planning and management. On the other hand, the construction of water harvesting structures changes the hydrological regime, affecting upstream-downstream dynamics and changing water allocation, often causing contentions. Furthermore, dynamics existing between water harvesting and water conflict are not properly investigated yet. Thus, objective of this study is to analyze the relations between water harvesting and the insurgence of water conflicts, providing a solid theoretical basis and foundations for future studies. Two search engines were selected in order to perform the study: Google Scholar and Scopus. Separate researches were conducted on the mutual influences between water conflicts and the four main water harvesting techniques: rooftop harvesting, surface harvesting, underground harvesting, runoff harvesting. Some of the aforementioned water harvesting techniques have been developed and implemented on scales ranging from the small, household-sided ones, to gargantuan dam systems. Instead of focusing on the collisions related to large-scale systems, this review is aimed to look for and collect examples of the effects that the implementation of small water harvesting systems has had on the access to the water resource and on water governance. The present research allowed to highlight that in the studies that have been conducted up to now, water harvesting, and in particular those structures that allow the collection and storage of water for domestic use, is usually recognized as a positive, palliative element during contentions. On the other hand, water harvesting can worsen and, in some cases, even generate conflicts for water management. This shows the necessity of studies that consider both benefits and negative influences of water harvesting, analyzing its role respectively as triggering or as mitigating factor of conflicting situations.

Keywords: arid areas, governance, water conflicts, water harvesting

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Authors: Kushal Patel, Manasa Dittakavi, Cyrus Falsafi, Gretchen Lovett

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Rural America has seen a surge in opioid addiction rates and overdose deaths in recent years, becoming a significant public health crisis. This may be due to a variety of factors, such as lack of access to healthcare or other economic and social factors that can contribute to addiction such as poverty, unemployment, and social isolation. As the opioid epidemic has disproportionately affected rural communities, pregnant women in these areas may be highly susceptible and face additional difficulties in facing the appropriate care they need. Opioid use disorder has many negative effects on prenatal infants. These include changes in their microbiome, mental health, neurodevelopment and cognition. These can affect how the child performs in various activities in life and how they interact with others. It has been demonstrated that using cognitive behavioral therapy improves not just pain-related results but also mobility, quality of life, disability, and mood outcomes. This indicates that cognitive behavioral therapy (CBT) may be a useful therapeutic strategy for enhancing general health and wellbeing in people with opioid use problems. In terms of treating psychiatric diseases, CBT carries fewer dangers than opioids. One study that illustrates the potential for CBT to promote a reduction in opioid use disorder used self-reported drug use patterns 6 months prior to and during their pregnancy. At the beginning of the study, participants reported an average of 3.78 drug or alcohol use days in the previous 28 days, which decreased to 1.63 days after treatment. The study also found a decrease in depression scores, as measured by IDS scores, from 23.9 to 17.1 at the end of treatment. These and other results show that CBT can have meaningful impacts on pregnant women in Rural America who struggle with an opioid use disorder. This project has been approved by the West Virginia School of Osteopathic Medicine- Office of Research and Sponsored Programs and deemed non-research scholarly work.

Keywords: appalachia, CBT, opiods, pregnancy

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Authors: Nicholas Pearce, Eun-jin Kim

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Pathologies of the cardiovascular (CV) system remain a serious and deadly health problem for human society. Computational modelling provides a relatively accessible tool for diagnosis, treatment, and research into CV disorders. However, numerical models of the CV system have largely focused on the function of the ventricles, frequently overlooking the behaviour of the atria. Furthermore, in the study of the pressure-volume relationship of the heart, which is a key diagnosis of cardiac vascular pathologies, previous works often evoke popular yet questionable time-varying elastance (TVE) method that imposes the pressure-volume relationship instead of calculating it consistently. Despite the convenience of the TVE method, there have been various indications of its limitations and the need for checking its validity in different scenarios. A model of the combined left ventricle (LV) and left atrium (LA) is presented, which consistently considers various feedback mechanisms in the heart without having to use the TVE method. Specifically, a synergistic model of the left ventricle is extended and modified to include the function of the LA. The synergy of the original model is preserved by modelling the electro-mechanical and chemical functions of the micro-scale myofiber for the LA and integrating it with the microscale and macro-organ-scale heart dynamics of the left ventricle and CV circulation. The atrioventricular node function is included and forms the conduction pathway for electrical signals between the atria and ventricle. The model reproduces the essential features of LA behaviour, such as the two-phase pressure-volume relationship and the classic figure of eight pressure-volume loops. Using this model, disorders in the internal cardiac electrical signalling are investigated by recreating the mechano-electric feedback (MEF), which is impossible where the time-varying elastance method is used. The effects of AV node block and slow conduction are then investigated in the presence of an atrial arrhythmia. It is found that electrical disorders and arrhythmia in the LA degrade the CV system by reducing the cardiac output, power, and heart rate.

Keywords: cardiovascular system, left atrium, numerical model, MEF

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Authors: Adel Alblihy, Reem Ali, Mashael Algethami, Ahmed Shoqafi, Michael S. Toss, Juliette Brownlie, Natalie J. Tatum, Ian Hickson, Paloma Ordonez Moran, Anna Grabowska, Jennie N. Jeyapalan, Nigel P. Mongan, Emad A. Rakha, Srinivasan Madhusudan

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Platinum resistance is a clinical challenge in ovarian cancer. Platinating agents induce DNA damage which activate Mre11 nuclease directed DNA damage signalling and response (DDR). Upregulation of DDR may promote chemotherapy resistance. Here we have comprehensively evaluated Mre11 in epithelial ovarian cancers. In clinical cohort that received platinum- based chemotherapy (n=331), Mre11 protein overexpression was associated with aggressive phenotype and poor progression free survival (PFS) (p=0.002). In the ovarian cancer genome atlas (TCGA) cohort (n=498), Mre11 gene amplification was observed in a subset of serous tumours (5%) which correlated highly with Mre11 mRNA levels (p<0.0001). Altered Mre11 levels was linked with genome wide alterations that can influence platinum sensitivity. At the transcriptomic level (n=1259), Mre11 overexpression was associated with poor PFS (p=0.003). ROC analysis showed an area under the curve (AUC) of 0.642 for response to platinum-based chemotherapy. Pre-clinically, Mre11 depletion by gene knock down or blockade by small molecule inhibitor (Mirin) reversed platinum resistance in ovarian cancer cells and in 3D spheroid models. Importantly, Mre11 inhibition was synthetically lethal in platinum sensitive XRCC1 deficient ovarian cancer cells and 3D-spheroids. Selective cytotoxicity was associated with DNA double strand break (DSB) accumulation, S-phase cell cycle arrest and increased apoptosis. We conclude that pharmaceutical development of Mre11 inhibitors is a viable clinical strategy for platinum sensitization and synthetic lethality in ovarian cancer.

Keywords: MRE11; XRCC1, ovarian cancer, platinum sensitization, synthetic lethality

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