Search results for: procurement strategy

Authors: K. Sushma Varma, Rajesh Singh

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Non-engineered landfills cause serious environmental damage due to toxic emissions and mobilization of persistent pollutants, organic and inorganic contaminants, as well as soluble metal ions. The available treatment technologies for landfill leachate and solid waste are not effective from an economic, environmental, and social standpoint. The present study assesses the potential of the bioelectrochemical system (BES) integrated with sulfate-reducing bacteria (SRB) in the sustainable treatment and decontamination of landfill wastes. For this purpose, solid waste and landfill leachate collected from different landfill sites were evaluated for long-term treatment using the integrated SRB-BES anaerobic designed bioreactors after pre-treatment. Based on periodic gas composition analysis, physicochemical characterization of the leachate and solid waste, and metal concentration determination, the present system demonstrated significant improvement in volumetric hydrogen production by suppressing methanogenesis. High reduction percentages of Be, Cr, Pb, Cd, Sb, Ni, Cr, COD, and sTOC removal were observed. This mineralization can be attributed to the synergistic effect of ammonia-assisted pre-treatment complexation and microbial sulphide formation. Despite being amended with 0.1N ammonia, the treated leachate level of NO³⁻ was found to be reduced along with SO₄²⁻. This integrated SRB-BES system can be recommended as an eco-friendly solution for landfill reclamation. The BES-treated solid waste was evidently more stabilized, as shown by a five-fold increase in surface area, and potentially useful for leachate immobilization and bio-fortification of agricultural fields. The vector arrangement and magnitude showed similar treatment with differences in magnitudes for both leachate and solid waste. These findings support the efficacy of SRB-BES in the treatment of landfill leachate and solid waste sustainably, inching a step closer to our sustainable development goals. It utilizes low-cost treatment, and anaerobic SRB adapted to landfill sites. This technology may prove to be a sustainable treatment strategy upon scaling up as its outcomes are two-pronged: landfill waste treatment and energy recovery.

Keywords: bio-electrochemical system, leachate /solid waste treatment, landfill leachate, sulfate-reducing bacteria

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Authors: Junaid Jibran Jawed, Prasanta Saini, Subrata Majumdar

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Background: Leishmania donovani infection causes severe host immune-suppression through the modulation of pathogen recognition receptors. Apart from TLRs (Toll Like Receptor), recent studies focus on the important contribution of NLR (NOD-Like Receptor) family member NOD1 and NOD2 as these receptors are capable of triggering host innate immunity. The aim of this study was to decipher the role of NOD1/NOD2 receptors during experimental visceral leishmaniasis (VL) and the important link between host failure and parasite evasion strategy. Method: The status of NOD1 and NOD2 receptors were analysed in uninfected and infected cells through western blotting and RT-PCR. The active contributions of these receptors in reducing parasite burden were confirmed by siRNA mediated silencing, and over-expression studies and the parasite numbers were calculated through microscopic examination of the Giemsa-stained slides. In-vivo studies were done by using non-toxic dose of Mw (Mycobacterium indicus pranii), Ara-LAM(Arabinoasylated lipoarabinomannan) along with MDP (Muramyl dipeptide) administration. Result: Leishmania donovani infection of the macrophages reduced the expression of NOD2 receptors whereas NOD1 remain unaffected. MDP, a NOD2-ligand, treatment during over-expression of NOD2, reduced the parasite burden effectively which was associated with increased pro-inflammatory cytokine generation and NO production. In experimental mouse model, Ara-LAM treatment increased the expression of NOD2 and in combination with MDP it showed active therapeutic potential against VL and found to be more effective than Mw which was already reported to be involved in NOD2 modulation. Conclusion: This work explores the essential contribution of NOD2 during experimental VL and mechanistic understanding of Ara-LAM + MDP combination therapy to work against this disease and highlighted NOD2 as an essential therapeutic target.

Keywords: Ara-LAM (Arabinoacylated Lipoarabinomannan), NOD2 (nucleotide binding oligomerization receptor 2), MDP (muramyl di peptide), visceral Leishmaniasis

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Authors: Abhisek Dash

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This study had three neural networks, one for number segmentation, one for number detection and one for number recognition all of which are coupled to one another. All networks were trained on the MNIST dataset and were convolutional. It was assumed that the images had lighter background and darker foreground. The segmentation network took 28x28 images as input and had sixteen outputs. Segmentation training starts when a dark pixel is encountered. Taking a window(7x7) over that pixel as focus, the eight neighborhood of the focus was checked for further dark pixels. The segmentation network was then trained to move in those directions which had dark pixels. To this end the segmentation network had 16 outputs. They were arranged as “go east”, ”don’t go east ”, “go south east”, “don’t go south east”, “go south”, “don’t go south” and so on w.r.t focus window. The focus window was resized into a 28x28 image and the network was trained to consider those neighborhoods which had dark pixels. The neighborhoods which had dark pixels were pushed into a queue in a particular order. The neighborhoods were then popped one at a time stitched to the existing partial image of the number one at a time and trained on which neighborhoods to consider when the new partial image was presented. The above process was repeated until the image was fully covered by the 7x7 neighborhoods and there were no more uncovered black pixels. During testing the network scans and looks for the first dark pixel. From here on the network predicts which neighborhoods to consider and segments the image. After this step the group of neighborhoods are passed into the detection network. The detection network took 28x28 images as input and had two outputs denoting whether a number was detected or not. Since the ground truth of the bounds of a number was known during training the detection network outputted in favor of number not found until the bounds were not met and vice versa. The recognition network was a standard CNN that also took 28x28 images and had 10 outputs for recognition of numbers from 0 to 9. This network was activated only when the detection network votes in favor of number detected. The above methodology could segment connected and overlapping numbers. Additionally the recognition unit was only invoked when a number was detected which minimized false positives. It also eliminated the need for rules of thumb as segmentation is learned. The strategy can also be extended to other characters as well.

Keywords: convolutional neural networks, OCR, text detection, text segmentation

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Authors: Abdelkrim Khadir, Sina Kavalakatt, Preethi Cherian, Ali Tiss

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Soluble epoxide hydrolase (sEH) is an emerging therapeutic target in several chronic states that have inflammation as a common underlying cause such as immunometabolic diseases. Indeed, sEH is known to play a pro-inflammatory role by metabolizing anti-inflammatory, epoxyeicosatrienoic acids (EETs) to pro-inflammatory diols. Recently, it was shown sEH to be linked to diet and microbiota interaction in rat models of obesity. Nevertheless, the functional contribution of sEH and its anti-inflammatory substrates EETs in obesity remain poorly understood. In the current study, we compared the expression pattern of sEH between lean and obese nondiabetic human subjects using subcutaneous adipose tissue (SAT) and peripheral blood mononuclear cells (PBMCs). Using RT-PCR, western blot and immunofluorescence confocal microscopy, we show here that the level of sEH mRNA and protein to be significantly increased in obese subjects with concomitant increase in endoplasmic reticulum (ER) stress components (GRP78 and ATF6α) and inflammatory markers (TNF-α, IL-6) when compared to lean controls. The observation that sEH was overexpressed in obese subjects’ prompt us to investigate whether physical exercise could reduce its expression. In this study, we report here 3-months supervised physical exercise significantly attenuated the expression of sEH in both the SAT and PBMCs, with a parallel decrease in the expression of ER stress markers along with attenuated inflammatory response. On the other hand, homocysteine, a sulfur containing amino acid deriving from the essential amino acid methionine was shown to be directly associated with insulin resistance. When 3T3-L1 preadipocytes cells were treated with homocysteine our results show increased sEH levels along with ER stress markers. Collectively, our data suggest that sEH upregulation is strongly linked to ER stress in adiposity and that physical exercise modulates its expression. This gives further evidence that exercise might be useful as a strategy for managing obesity and preventing its associated complications.

Keywords: obesity, adipose tissue, epoxide hydrolase, ER stress

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Authors: Chenhao Zhu

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Quantitative mapping is playing a growing role in guiding urban planning, such as using a heat map created by CFX, CFD2000, or Envi-met, to adjust the master plan. However, there is no effective quantitative link between the mappings and planning formation. So, in many cases, the decision-making is still based on the planner's subjective interpretation and understanding of these mappings, which limits the improvement of scientific and accuracy brought by the quantitative mapping. Therefore, in this paper, an effort has been made to give a methodology of building a parametric link between the mapping and planning formation. A parametric planning process based on radiant mapping has been proposed for creating an urban green system. In the first step, a script is written in Grasshopper to build a road network and form the block, while the Ladybug Plug-in is used to conduct a radiant analysis in the form of mapping. Then, the research creatively transforms the radiant mapping from a polygon into a data point matrix, because polygon is hard to engage in the design formation. Next, another script is created to select the main green spaces from the road network based on the criteria of radiant intensity and connect the green spaces' central points to generate a green corridor. After that, a control parameter is introduced to adjust the corridor's form based on the radiant intensity. Finally, a green system containing greenspace and green corridor is generated under the quantitative control of the data matrix. The designer only needs to modify the control parameter according to the relevant research results and actual conditions to realize the optimization of the green system. This method can also be applied to much other mapping-based analysis, such as wind environment analysis, thermal environment analysis, and even environmental sensitivity analysis. The parameterized link between the mapping and planning will bring about a more accurate, objective, and scientific planning.

Keywords: parametric link, mapping, urban green system, radiant intensity, planning strategy, grasshopper

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Authors: Anshu Gupta, Charu Gupta

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Background: Punjab, a border state in India has achieved notoriety world over for its drug abuse problem. People right from school kids to elderly are hooked to drugs. This pattern of substance abuse is prevalent in both cities and villages alike. Excess of younger population in India has further aggravated the situation. It is feared that the benefits of India’s economic growth may well be negated by the rising substance abuse especially in this part of the country. It is quite evident that the pattern of substance abuse tends to change over time which is an impediment in the formulation of effective strategies to tackle this issue. Aim: Purpose of the study was to ascertain the change in the pattern of drug abuse for two consecutive years in the out patient department (OPD) population. Method: The study population comprised of all the patients reporting for deaddiction to the psychiatry outpatient department over a period of twelve months for two consecutive years. All the patients were evaluated by the International Classification of Diseases; 10 criteria for substance abuse/dependence. Results: A considerably high prevalence of substance abuse was present in the Indian population. In general, there was an increase in prevalence from first to the second year, especially among the female population. Increase in prevalence of substance abuse appeared to be more prominent among the younger age group of both the sexes. A significant increase in intravenous drug abuse was observed. Peer pressure and parental imitation were the major factors fueling substance abuse. Precipitation or fear of withdrawal symptoms was the major factor preventing abstinence. Substance abuse had a significant effect on the health and interpersonal relations of these patients. Summary/Conclusion: Drug abuse and addiction are on the rise throughout India. Changing cultural values, increasing economic stress and dwindling supportive bonds appear to be leading to initiation of substance abuse. Need of the hour is to formulate a comprehensive strategy to bring about an overall reduction in the use of drugs.

Keywords: deaddiction, peer pressure, parental imitation, substance abuse/dependance

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Authors: Hassan Nour, Nouh Mounadi, Oussama Abchir, Belaidi Salah, Samir Chtita

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Cholinesterase enzymes are biological catalysts essential for the transformation of acetylcholine, which is a neurotransmitter implicated in memory and learning, into acetic acid and choline, altering the neurotransmission process in Alzheimer’s disease patients. Therefore, inhibition of cholinesterase enzymes is a relevant strategy for the symptomatic treatment of Alzheimer’s disease. The current investigation aims to explore potential cholinesterase (ChE) inhibitors through a comprehensive computational approach. Forty-nine phytoconstituents extracted from Cannabis sativa L. were in-silico screened using molecular docking and pharmacokinetic and toxicological analysis to evaluate their possible inhibitory effect on the cholinesterase enzymes. Two phytoconstituents belonging to cannabinoid derivatives were revealed to be promising candidates for Alzheimer's therapy by acting as cholinesterase inhibitors. They have exhibited high binding affinities towards the cholinesterase enzymes and showed their ability to interact with key residues involved in cholinesterase enzymatic activity. In addition, they presented good ADMET profiles allowing them to be promising oral drug candidates. Furthermore, molecular dynamics (MD) simulations were executed to explore their interaction stability under mimetic biological conditions and thus support our findings. To corroborate the docking results, the binding free energy corresponding to the more stable ligand-ChE complexes was re-estimated by applying the MM-PBSA method. MD and MM-PBSA studies affirmed that the ligand-ChE recognition is a spontaneous reaction leading to stable complexes. The conducted investigations have led to great findings that would strongly guide the pharmaceutical industries toward the rational development of potent anti-Alzheimer agents.

Keywords: Alzheimer’s disease, molecular docking, Cannabis sativa L., cholinesterase inhibitors, molecular dynamics, ADMET, MM-PBSA

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Authors: Armando T. Zúñiga

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As the number of English Language Learners (ELLs) in public schools continues to grow, so does the achievement gap between ELLs and other student populations. In an effort to support classroom teachers with effective instructional strategies for this student population, many districts have created instructional coaching positions specifically to support classroom teachers of ELLs—ELL Teachers on Special Assignment (ELL TOSAs). This study employed a gap analysis framework to the ELL TOSA professional support program in one California school district to examine knowledge, motivation, and organizational influences (KMO) on the ELL TOSAs’ goal of supporting classroom teachers of ELLs. Three themes emerged as a result of data analysis. First, there was evidence to illustrate the interaction between knowledge and the organization. Data from ELL TOSAs indicated an understanding of the role that collaboration plays in coaching and how to operationalize it in their support of teachers. Further, all of the ELL TOSAs indicated they have received professional development on effective strategies for instructional coaching. Additionally, a large percentage of the ELL TOSAs indicated a knowledge of modeling as an effective coaching practice. Accordingly, all of the ELL TOSAs indicated that they had knowledge of feedback as an effective coaching strategy. However, there was not sufficient evidence to support that they learned the latter two strategies through professional development. A second theme surfaced as there was evidence to illustrate an interaction between motivation and the organization. Some ELL TOSAs indicated that their sense of self-efficacy was affected by conflicting roles and expectations for the job. Most of the ELL TOSAs indicated that their sense of self-efficacy was affected by an increased workload brought about by fiscal decision making. Finally, there was evidence illustrating the interaction between the organization and motivation. The majority of the of ELL TOSAs indicated that there is confusion about how their roles are perceived, leaving the ELL TOSAs to feel that their actions did not contribute to instructional change. In conclusion, five research-based recommendations to support ELL TOSA goal attainment and considerations for future research on instructional coaches for classroom teachers of ELLs are provided.

Keywords: English language development, English language acquisition, language and leadership, language coaching, English language learners, second language acquisition

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Authors: Naznine Anwar, Kim Cornish, Izelle Labuschagne, Nellie Georgiou-Karistianis

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Falls and subsequent injuries are common features in symptomatic Huntington’s disease (symp-HD) individuals. As part of daily walking, navigating around obstacles may incur a greater risk of falls in symp-HD. We designed obstacle-crossing experiment to examine adaptive gait dynamics and to identify underlying spatiotemporal gait characteristics that could increase the risk of falling in symp-HD. This experiment involved navigating around one or two ground-based obstacles under two conditions (walking while navigating around one obstacle, and walking while navigating around two obstacles). A total of 32 participants were included, 16 symp-HD and 16 healthy controls with age and sex matched. We used a GAITRite electronic walkway to examine the spatiotemporal gait characteristics and inter-trail gait variability when participants walked at their preferable speed. A minimum of six trials were completed which were performed for baseline free walk and also for each and every condition during navigating around the obstacles. For analysis, we separated all walking steps into three phases as approach steps, navigating steps and recovery steps. The mean and inter-trail variability (within participant standard deviation) for each step gait variable was calculated across the six trails. We found symp-HD individuals significantly decreased their gait velocity and step length and increased step duration variability during the navigating steps and recovery steps compared with approach steps. In contrast, HC individuals showed less difference in gait velocity, step time and step length variability from baseline in both respective conditions as well as all three approaches. These findings indicate that increasing spatiotemporal gait variability may be a possible compensatory strategy that is adopted by symp-HD individuals to effectively navigate obstacles during walking. Such findings may offer benefit to clinicians in the development of strategies for HD individuals to improve functional outcomes in the home and hospital based rehabilitation program.

Keywords: Huntington’s disease, gait variables, navigating around obstacle, basal ganglia dysfunction

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Authors: Masome Moeni, Roya Abedizadeh, Elham Aram, Hamid Sadeghi-Abandansari, Davood Sabour, Robert Menzel, Ali Hassanpour

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Mitochondria- targeting immunogenic cell death inducers (MT-ICD) have been designed to trigger intrinsic apoptosis signalling pathway in malignant cells and revive the antitumour immune system. MT-ICD inducers have considered to be non-specific, which can deteriorate the ability to initiate mitochondria-selective oxidative stress, causing high toxicity. Iron oxide nanoparticles (IONPs) can be an ideal candidate as vehicles for utilizing in immunotherapy due to their biocompatibility, modifiable surface chemistry, magnetic characteristics and multi-functional applications in single platform. These types of NPs can facilitate a real time imaging which can provide an effective strategy to analyse pharmacokinetic parameters of nano-formula, including blood circulation time, targeted and controlled release at tumour microenvironment. To our knowledge, the conjugation of IONPs with MT-ICD and oxaliplatin (a chemotherapeutic agent used for the treatment of colorectal cancer) for immunotherapy have not been investigated. Herein, IONPs were generated via co-precipitation reaction at high temperatures, followed by coating the colloidal suspension with tetraethyl orthosilicate and 3-aminopropyltriethoxysilane to optimize their bio-compatibility, preventing aggregation and maintaining stability at physiological pH, then functionalized with (3-carboxypropyl) triphenyl phosphonium bromide for mitochondrial delivery. Analytical results demonstrated the successful process of IONPs functionalization. In particular, the colloidal particles of doped IONPs exhibited an excellent stability and dispersibility. The resultant particles were also successfully loaded with the oxaliplatin for an active mitochondrial targeting in immunotherapy, resulting in well-maintained super-paramagnetic characteristics and stable structure of the functionalized IONPs with nanoscale particle sizes.

Keywords: Immunotherapy, mitochondria, cancer, iron oxide nanoparticle

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Authors: Waepa Wanhussen

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The Ministry of Public Health has established policies accelerating health promotion to prevent public health problems in five border provinces of Thailand. One of these policies employs the religion to guide the community development and solve health issues consistent with the lifestyle and culture of those people. This policy is an important strategy to solve the problems due to the unrest and conflicts in the southern border provinces. This participatory action research aimed to develop mosques as healthy religion places in Narathiwat Province. In the development, the participatory action, consisting of 5 stages, was conducted from October 2012 - May 2013. Stage I: Conducting a survey for problems and needs for developing healthy religion places by employing community participation. Stage II: Analyzing problems and situations at a workshop containing informal interviews and group conversations with 200 participants (health providers at district level, Imams (the Muslim leaders), and community leaders). Stage III: Planning for developing healthy religion places by health providers, Imams, community leaders. Stage IV: Implementing the plan according to the conditions of problems and needs of the community in order to develop healthy religion places. Stage V: Evaluating the implementation by using the instrument, a criteria of being healthy religion place, for collecting data. Data were analyzed by using percentage. It was found that out of 630 mosques 575 (90.12%) passed the criteria of being a healthy religion place. Among these mosques, 190 mosques (30.15%) were in good and very good level, in which, after the implementation, the number of being good and very good healthy mosques increased by 22.58%. The researcher suggested that the developing sustainably healthy religion places require the participation of residences in the community and agencies such as local government, the Islamic Council of Narathiwat Province, and Council of Culture of Narathiwat Province. The healthy religion places can be used to strengthen and sustain health promotion and disease prevention in the community as health learning centers.

Keywords: healthy religion places, development of community participation, nursing informatics, health

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Authors: Nagendra P. Luitel, Mark J. D. Jordans

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Globally, there is a significant gap between the number of individuals in need of mental health care and those who actually receive treatment. The evidence is accumulating that mental health services can be delivered effectively by primary health care workers through community-based programs and task-sharing approaches. Changing the role of specialist mental health workers from service delivery to building clinical capacity of the primary health care (PHC) workers could help in reducing treatment gap in low and middle-income countries (LMICs). We developed a comprehensive mental health care plan in 2012 and evaluated its feasibility and effectiveness over the past three years. Initially, a mixed method formative study was conducted for the development of mental health care plan (MHCP). Routine monitoring and evaluation data, including client flow and reports of satisfaction, were obtained from beneficiaries (n=135) during the pilot-testing phase. Repeated community survey (N=2040); facility detection survey (N=4704) and the cohort study (N=576) were conducted for evaluation of the MHCP. The resulting MHCP consists of twelve packages divided over the community, health facility, and healthcare organization platforms. Detection of mental health problems increased significantly after introducing MHCP. Service implementation data support the real-life applicability of the MHCP, with reasonable treatment uptake. Currently, MHCP has been implemented in the entire Chitwan district where over 1400 people (438 people with depression, 406 people with psychosis, 181 people with epilepsy, 360 people with alcohol use disorder and 51 others) have received mental health services from trained health workers. Key barriers were identified and addressed, namely dissatisfaction with privacy, perceived burden among health workers, high drop-out rates and continue the supply of medicines. The results indicated that involvement of PHC workers in detection and management of mental health problems is an effective strategy to minimize treatment gap on mental health care in Nepal.

Keywords: mental health, Nepal, primary care, treatment gap

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Authors: Maria Monica D. Espinosa

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This study aimed to identify and examine the characteristics of an effective leader in a Hospital institution from the perspectives of military nurse-managers. The researcher extracted the different facets of leadership from the stories of six nurse- managers from a military hospital. The stories which are in pre-reflective stage convey an unbiased perspective from which clinical leadership may be defined. Using Phenomenology as a method of Research, the lived experiences of the military nurse-managers served as empirical data which were reflected upon until the formulation of insights. The information from the co-researchers became gallows from which the characteristics of effective leadership in the clinical area were drawn. These insights were synthesized through layers of reflection that resulted to the knowledge about clinical leadership. The reflections are the following, (a) Clinical leaders develop their skills through experiences and hardwork; (b) Clinical leaders are devoted; (c) Clinical leaders are focused; (d) Clinical leaders are good in interpersonal relationship; (e) Clinical leaders are mentors; (f) Clinical leaders seek affirmation and recognition; and (g) Clinical leaders are responsible and dependable. The common themes that emerged from the nurse manager’s stories showed that clinical leadership maybe attained if leaders possessed the following traits, (a) The gift to establish a steadfast and firm management; (b) The proficiency to guide and encourage others towards the achievement of their goals and objectives; (c) The ability to instigate participative and collaborative work among his/her subordinates and (d) The aptitude and skill to address the institutional concerns in their unit. In the future, Clinical leaders should continually adapt an evaluation program on how they can relate socially with their subordinates, the result of which can be used as a basis in developing strategies on relationship enhancement. Moreover, they should empower the nurses by allowing them to voice out their opinions and concerns regarding assignments, role expectations, and workload issues to improve and strengthen the relationships among nurses. Lastly, they can incorporate a collaborative strategy to promote professional socialization attitudes of nurse managers who work with staff nurses to improve the quality of their proficiencies and enhance a positive clinical environment.

Keywords: clinical leadership, experiences, implications, military nurse - managers, phenomenology

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Authors: Atiwit Sinyoo, Sekh Thanprasertsuk, Sithiporn Agthong, Pasakorn Watanatada, Shaun Peter Qureshi, Saknan Bongsebandhu-Phubhakdi

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Background: Since the SARS-CoV-2 virus became extensively disseminated throughout the world, online learning has become one of the most hotly debated topics in educational reform. While some studies have already shown the advantage of online learning, there are still questions concerning how online learning affects students’ learning behavior and academic achievement when each student learns in a different way. Hence, we aimed to develop a guide for preclinical medical students to avoid drawbacks and get benefits from online learning that possibly a double-edged sword. Methods: We used a multiple-choice questionnaire to evaluate the learning behavior of second-year Thai medical students in the neuroscience course. All traditional face-to-face lecture classes were video-recorded and promptly posted to the online learning platform throughout this course. Students could pick and choose whatever classes they wanted to attend, and they may use online learning as often as they wished. Academic performance was evaluated as summative score, spot exam score and pre-post-test improvement. Results: More frequently students used online learning platform, the less they attended lecture classes (P = 0.035). High proactive online learners (High PO) who were irregular attendee (IrA) had significantly lower summative scores (P = 0.026), spot exam score (P = 0.012) and pre-post-test improvement (P = 0.036). In the meanwhile, conditional attendees (CoA) who only attended classes with attendance check had significantly higher summative score (P = 0.025) and spot exam score (P = 0.001) if they were in the High PO group. Conclusions: The benefit and drawbacks edges of using an online learning platform were demonstrated in our research. Based on this double-edged sword effect, we believe that online learning is a valuable learning strategy, but students must carefully plan their study schedule to gain the “benefit edge” meanwhile avoiding its “drawback edge”.

Keywords: academic performance, assessment, attendance, online learning, preclinical medical students

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Authors: Abrha Ybeyn Gebremedhn, Yitea Seneshaw Getahun, Alebachew Shumye Moges, Fikrey Tesfay

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Rainfed agriculture in Ethiopia has failed to produce enough food, to achieve the increasing demand for food. Pinpointing the appropriate site for rainwater harvesting (RWH) have a substantial contribution to increasing the available water and enhancing agricultural productivity. The current study related to the identification of the potential RWH sites was conducted at the Chacha watershed central highlands of Ethiopia which is endowed with rugged topography. The Geographic Information System with Analytical Hierarchy Process was used to generate the different maps for identifying appropriate sites for RWH. In this study, 11 factors that determine the RWH locations including slope, soil texture, runoff depth, land cover type, annual average rainfall, drainage density, lineament intensity, hydrologic soil group, antecedent moisture content, and distance to the roads were considered. The overall analyzed result shows that 10.50%, 71.10%, 17.90%, and 0.50% of the areas were found under highly, moderately, marginally suitable, and unsuitable areas for RWH, respectively. The RWH site selection was found highly dependent on a slope, soil texture, and runoff depth; moderately dependent on drainage density, annual average rainfall, and land use land cover; but less dependent on the other factors. The highly suitable areas for rainwater harvesting expansion are lands having a flat topography with a soil textural class of high-water holding capacity that can produce high runoff depth. The application of this study could be a baseline for planners and decision-makers and support any strategy adoption for appropriate RWH site selection.

Keywords: runoff depth, antecedent moisture condition, AHP, weighted overlay, water resource

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Authors: Anum Obaid, Bushra Noor, Zoshia Zainab

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In South Asian countries, Pakistan faces significant public health challenges regarding maternal and neonatal health (MNH). Despite global efforts to improve maternal, newborn, child, and health (MNCH) outcomes through initiatives like the Millennium Development Goals (MDGs) and Sustainable Development Goals (SDGs), high maternal and neonatal mortality rates persist. In patriarchal societies, cultural norms, family dynamics, and gender roles heavily influence healthcare accessibility and decision-making processes, often leading to delayed and inadequate maternal care. Addressing these socio-cultural barriers and enhancing healthcare resources is crucial to improving maternal health outcomes in areas like Faisalabad. A qualitative study was conducted involving two groups of informants: gynecologists practicing in private clinics and first-time pregnant women receiving care in government hospitals. Data collection included obtaining institutional permission, conducting semi-structured in-depth interviews, and using non-probability sampling techniques. A proactive strategy to overcome maternal health challenges involves using aversion therapy and disseminating knowledge among family members. This approach aims to foster a deep understanding within the family unit regarding the importance of maternal well-being, thereby creating a supportive environment and facilitating informed decision-making related to healthcare access and lifestyle choices. The findings indicate that maternal health is compromised both physiologically and psychologically, with significant implications for the baby's health. Mental well-being is profoundly affected, largely due to familial behavior and entrenched cultural taboos.

Keywords: maternal health, neonatal health, socio-cultural norms, primigravida women, gynecologist, familial conduct, cultural taboos

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Authors: T. Iakovleva

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Present paper suggests a theoretical model that describes the process of the development of responsible innovations on the firm level in health and welfare sectors. There is a need to develop new firm strategies in these sectors. This paper suggests to look on the concept of responsible innovation that was originally developed on the social level and to apply this new concept to the new area of firm strategy. The rapid global diffusion of information and communication technologies has greatly improved access to knowledge. At the same time, communication is cheap, information is a commodity, and global trade increases technological diffusion. As a result, firms and users, including those outside of industrialized nations, get early exposure to the latest technologies and information. General-purpose technologies such as mobile phones and 3D printers enable individuals to solve local needs and customize products. The combined effect of these changes is having a profound impact on the innovation landscape. Meanwhile, the healthcare sector is facing unprecedented challenges, which are magnified by budgetary constraints, an aging population and the desire to provide care for all. On the other hand, patients themselves are changing. They are savvier about their diseases, they expect their relation with the healthcare professionals to be open and interactive, but above all they want to be part of the decision process. All of this is a reflection of what is already happening in other industries where customers have access to large amount of information and became educated buyers. This article addresses the question of how ICT research and innovation may contribute to developing solutions to grand societal challenges in a responsible way. A broad definition of the concept of responsibility in the context of innovation is adopted in this paper. Responsibility is thus seen as a collective, uncertain and future-oriented activity. This opens the questions of how responsibilities are perceived and distributed and how innovation and science can be governed and stewarded towards socially desirable and acceptable ends. This article addresses a central question confronting politicians, business leaders, and regional planners.

Keywords: responsible innovation, ICT, healthcare, welfare sector

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Authors: Syeda Sahra, Abdullah Jahangir, Rachelle Hamadi, Ahmad Jahangir, Allison Glaser

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Background: Antimicrobial resistance is on the rise. The use of redundant and inappropriate antibiotics is contributing to recurrent infections and resistance. Newer antibiotics with more robust coverage for gram-negative bacteria are in great demand for complicated urinary tract infections (cUTIs), complicated intra-abdominal infections (cIAIs), hospital-acquired bacterial pneumonia (H.A.B.P.), and ventilator-associated bacterial pneumonia (V.A.B.P.). Objective: We performed this meta-analysis to evaluate the efficacy and safety profile of a new antibiotic, Imipenem/cilastatin/relebactam, compared to other broad-spectrum antibiotics for complicated infections. Search Strategy: We conducted a systemic review search on PubMed, Embase, and Central Cochrane Registry. Selection Criteria: We included randomized clinical trials (R.C.T.s) with the standard of care as comparator arm with Imipenem/cilastatin/relebactam as intervention arm. Analysis: For continuous variables, the mean difference was used. For discrete variables, we used the odds ratio. For effect sizes, we used a confidence interval of 95%. A p-value of less than 0.05 was used for statistical significance. Analysis was done using a random-effects model irrespective of heterogeneity. Heterogeneity was evaluated using the I2 statistic. Results: The authors observed similar efficacy at clinical and microbiologic response levels on early follow-up and late follow-up compared to the established standard of care. The incidence of drug-related adverse events, serious adverse events, and drug discontinuation due to adverse events were comparable across both groups. Conclusion: Imipenem/cilastatin/relebactam has a non-inferior safety and efficacy profile compared to peer antibiotics to treat severe bacterial infections (cUTIs, cIAIs, H.A.B.P., V.A.B.P.).

Keywords: bacterial pneumonia, complicated intra-abdominal infections, complicated urinary tract infection, Imipenem, cilastatin, relebactam

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Authors: Lauren C. Porter, Andrew Curtis, Eric Jefferis, Susanne Mitchell

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A wealth of research has been generated examining the variation in crime across neighborhoods. However, there is also a striking degree of crime concentration within neighborhoods. A number of studies show that a small percentage of street segments, intersections, or addresses account for a large portion of crime. Not surprisingly, a focus on these crime hot spots can be an effective strategy for reducing community level crime and related ills, such as health problems. However, research is also limited in an important respect. Studies tend to use official data to identify hot spots, such as 911 calls or calls for service. While the use of call data may be more representative of the actual level and distribution of crime than some other official measures (e.g. arrest data), call data still suffer from the 'dark figure of crime.' That is, there is most certainly a degree of error between crimes that occur versus crimes that are reported to the police. In this study, we present an alternative method of identifying crime hot spots, that does not rely on official data. In doing so, we highlight the potential utility of neighborhood-insiders to identify and understand crime dynamics within geographic spaces. Specifically, we use spatial video and geo-narratives to record the crime insights of 36 police, ex-offenders, and residents of a high crime neighborhood in northeast Ohio. Spatial mentions of crime are mapped to identify participant-identified hot spots, and these are juxtaposed with calls for service (CFS) data. While there are bound to be differences between these two sources of data, we find that one location, in particular, a corner store, emerges as a hot spot for all three groups of participants. Yet it does not emerge when we examine CFS data. A closer examination of the space around this corner store and a qualitative analysis of narrative data reveal important clues as to why this store may indeed be a hot spot, but not generate disproportionate calls to the police. In short, our results suggest that researchers who rely solely on official data to study crime hot spots may risk missing some of the most dangerous places.

Keywords: crime, narrative, video, neighborhood

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Authors: M. Lobzhanidze, N. Damenia

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The article analyzes the current structural changes in the economy of Georgia, liberalization and integration processes of the economy. In accordance with this analysis, the peculiarities and the problems of youth employment are revealed. In the paper, the Georgian labor market and its contradictions are studied. Based on the analysis of materials, the socio-economic losses caused by the long-term and mass unemployment of young people are revealed, the objective and subjective circumstances of getting higher education are studied. The youth employment and unemployment rates are analyzed. Based on the research, the factors that increase unemployment are identified. According to the analysis of the youth employment, it has appeared that the unemployment share in the number of economically active population has increased in the younger age group. It demonstrates the high requirements of the labour market in terms of the quality of the workforce. Also, it is highlighted that young people are exposed to a highly paid job. The following research methods are applied in the presented paper: statistical (selection, grouping, observation, trend, etc.) and qualitative research (in-depth interview), as well as analysis, induction and comparison methods. The article presents the data by the National Statistics Office of Georgia and the Ministry of Agriculture of Georgia, policy documents of the Parliament of Georgia, scientific papers by Georgian and foreign scientists, analytical reports, publications and EU research materials on similar issues. The work estimates the students and graduates employment problems existing in the state development strategy and priorities. The measures to overcome the challenges are defined. The article describes the mechanisms of state regulation of youth employment and the ways of improving this regulatory base. As for major findings, it should be highlighted that the main problems are: lack of experience and incompatibility of youth qualification with the requirements of the labor market. Accordingly, it is concluded that the unemployment rate of young people in Georgia is increasing.

Keywords: migration of youth, youth employment, migration management, youth employment and unemployment

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Authors: James Barmby

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Canada’s westernmost provinces of British Columbia and Alberta are similar in many respects as they are both reliant on volatile natural resources for major portions of their economies. The two provinces have banded together to develop mutually beneficial trade, investment and labour market mobility rules, but in terms of developing systems of higher education, the two provinces are attempting to align higher education programs to economic development objectives by means that are quite different. In British Columbia, the recently announced initiative, B.C’s Skills for Jobs Blueprint will “make sure education and training programs are aligned with the demands of the labor market.” Meanwhile in Alberta, the province’s institutions of higher education are enjoying the tenth year of their membership in the Campus Alberta Quality Council, which makes recommendations to government on issues related to post-secondary education, including the approval of new programs. In B.C., public institutions of higher education are encouraged to comply with government objectives, and are rewarded with targeted funds for their efforts. In Alberta, the institutions as a system tell the government what programs they want to offer and government can agree or not agree to fund these programs through a ministerial approval process. In comparing the two higher education systems, the question emerges as to which one is more beneficial to the province: the one where change is directed primarily by financial incentives to achieve economic objectives or the one that makes recommendations to the government for changes in programs to achieve institutional objectives? How is institutional autonomy affected in each strategy? Does institutional autonomy matter anymore? In recent years, much has been written in regard to academic freedom, but less about institutional autonomy, which is seen by many as essential to protecting academic freedom. However, while institutional autonomy means freedom from government control, it does not necessarily mean self-government. In this study, a comparison of the two higher education systems is made using recent government policy initiatives in both provinces, and responses to those actions by the higher education institutions. The findings indicate that the economic needs in both provinces take precedence over issues of institutional autonomy.

Keywords: alberta, British Columbia, institutional autonomy, funding

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Authors: Amlakie Nigussie Assefa, Jemal Mohammed Haile, Amanuel Gebru Woldearegay

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Childhood vaccination communication is an important strategy to promote child immunization. This study was conducted with the objective of examining mothers’/caregivers’ perceptions of the child vaccine communication practice in the Amhara Region of Ethiopia. The researchers employed a quantitative research design to achieve the objective. A pretested questionnaire was used to collect the required data. The quantitative method was used to analyze the data. To this end, the result of the one-sample t-test revealed that mothers/caregivers perceive that child vaccine communication is irrelevant, indicated by the average mean of 13.11<15 of the expected mean. The finding also indicated that interpersonal health communication principles were not applied, which is indicated by the average mean of 16.82<18 of the ideal mean. The independent sample t-test underscored that knowledge about vaccines has an impact on the perceived relevance of child vaccine communication (Yes: M=16.55 SD=6.323; No: M=9.24, SD=4.087) (F=97.150 p=0.000, p<0.05), and the implementation of interpersonal health communication principals (M=18.65, SD=5.517; No: (M=9.81, SD=4.491) (F=11.015, p=0.000, p<0.05). The analysis of variance showed that mothers /caregivers’ education level has an impact on the perceived relevance of child vaccine communication (F=3.844 p=0.004, p<0.05) and to the implementation of interpersonal health communication principles (F=6.334 p=0.000, p<0.05). Besides, the post-hoc test showed that the respondents’ in the “Other” education level category have a positive perception to the relevance of child vaccine communication ((M=4.2 p= 0.006, p<0.05) and to the implementation of interpersonal health communication principles (M=3.5 p=0.000, p<0.05). The correlation analysis shows that education level has a positive correlation with the perceived relevance of child vaccine communication (r =0.198, p=0.00, P<0.01) and with the perceived implementation of interpersonal health communication principles (r = 0.250, p = 0.000 p< 0.01). Furthermore, one-to-one, one-to-group, and door-to-door communication were the most preferred strategies used to communicate about child vaccines. What is more, health workers were the most trusted sources of child vaccine information. In conclusion, the study highlighted that mothers/caregivers did not have a positive view of the child vaccine communication. Hence, efforts have to be made to improve mothers’/caregivers' knowledge about child vaccines. Besides, the education level of mothers/caregivers should be taken into consideration during the implementation of child vaccine communication interventions.

Keywords: mothers’/caregivers' perception, child vaccine communication, preferred communication strategies, trusted sources

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Authors: Eiman A. Al-Enezi, Gin Jose, Sikha Saha, Paul Millner

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Rare earth nanotechnology has gained a considerable amount of interest in the field of biosensing due to the unique luminescence properties of lanthanides. Chelating rare earth ions plays a significant role in biological labelling applications including medical diagnostics, due to their different excitation and emission wavelengths, variety of their spectral properties, sharp emission peaks and long fluorescence lifetimes. We aimed to develop a platform for biosensors based on Europium (Eu³⁺) chelates against biomarkers of cardiac injury (heart-type fatty acid binding protein; H-FABP3) and stroke (glial fibrillary acidic protein; GFAP). Additional novelty in this project is the use of synthetic binding proteins (Affimers), which could offer an excellent alternative targeting strategy to the existing antibodies. Anti-GFAP and anti-HFABP3 Affimer binders were modified to increase the number of carboxy functionalities. Europium nitrate then incubated with the modified Affimer. The luminescence characteristics of the Eu³⁺ complex with modified Affimers and antibodies against anti-GFAP and anti-HFABP3 were measured against different concentrations of the respective analytes on excitation wavelength of 395nm. Bovine serum albumin (BSA) was used as a control against the IgG/Affimer Eu³⁺ complexes. The emission spectrum of Eu³⁺ complex resulted in 5 emission peaks ranging between 550-750 nm with the highest intensity peaks were at 592 and 698 nm. The fluorescence intensity of Eu³⁺ chelates with the modified Affimer or antibodies increased significantly by 4-7 folder compared to the emission spectrum of Eu³⁺ complex. The fluorescence intensity of the Affimer complex was quenched proportionally with increased analyte concentration, but this did not occur with antibody complex. In contrast, the fluorescence intensity for Eu³⁺ complex increased slightly against increased concentration of BSA. These data demonstrate that modified Affimers Eu³⁺ complexes can function as nanobiosensors with potential diagnostic and analytical applications.

Keywords: lanthanides, europium, chelates, biosensors

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Authors: Tingyu Zhang

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The cross-basin ecological compensation mechanism is key to stimulating active participation in ecological protection across the entire basin. This study constructs an evolutionary game model of cross-basin ecological compensation in the Yangtze River Economic Belt (YREB), introducing a central government constraint and incentive mechanism (CGCIM) to explore the conditions for achieving strategies of protection and compensation that meet societal expectations. Furthermore, using a water quality-water quantity model combined with factual data from the YREB in 2020, the amount of ecological compensation is calculated. The results indicate that the stability of the evolutionary game model of the upstream and downstream governments in the YREB is closely related to the CGCIM. When the sum of the central government's reward amount to the upstream government and the penalty amount to both sides simultaneously is greater than 39.948 billion yuan, and the sum of the reward amount to the downstream government and the penalty amount to only the lower reaches is greater than 1.567 billion yuan, or when the sum of the reward amount to the downstream government and the penalty amount to both sides simultaneously is greater than 1.567 billion yuan, and the sum of the reward amount to the upstream government and the penalty amount to only the upstream government is greater than 399.48 billion yuan, the protection and compensation become the only evolutionarily stable strategy for the evolutionary game system composed of the upstream and downstream governments in the YREB. At this point, the total ecological compensation that the downstream government of the YREB should pay to the upstream government is 1.567 billion yuan, with Hunan paying 0.03 billion yuan, Hubei 2.53 billion yuan, Jiangxi 0.18 billion yuan, Anhui 1.68 billion yuan, Zhejiang 0.75 billion yuan, Jiangsu 6.57 billion yuan, and Shanghai 3.93 billion yuan. The research results can provide a reference for promoting the improvement and perfection of the cross-basin ecological compensation system in the YREB.

Keywords: ecological compensation, evolutionary game model, central government constraint and incentive mechanism, Yangtze river economic belt

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Authors: Aisha Iddrsiu

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Public Relations (PR) has rapidly evolved around the world, just as companies have expanded to reach other parts of the world. With most multinational corporations conducting businesses in more than one country, only a few of these Multinational Corporations (MNC’s) are actual public relations firms, many have public relations departments or divisions that conduct public relations practices internationally. Hence international public relations is seen as a fast-growing specialty in the field of Public Relations. Multinational companies have devised strategies to effectively communicate and execute their roles within and between foreign publics and other cultures in which they operate through various means including the internet which is among the major inventions that have enabled corporations to establish their presents while targeting anonymous and diverse publics from varied cultures. International public relations practitioners rely on strategies coupled with internet use to communicate among and with foreign publics. Corporate websites and various social media handles have served as an important channel for public relations activities targeting both internal and international publics. In an incessant expansion of corporations and interactions with the publics from different cultures, it has become eminent to understand the public relation strategies used by MNCs in their international communication. This study therefore seeks to establish the international public relation strategies or models employed by Multinational Corporations specifically Arcelik Global in the management of its subsidiaries and communicating with international public. This study analyses both Arçelik global’s (one of the largest multinational companies in Turkey) website and social media accounts to understand the management strategy used with it subsidiary as well as strategies used to communicate with its global and local publics. Other underlying objective of this study are, 1. To examine the dominant international public relations models used by Multinational Corporations (Arcelik global). 2. To understand how Multinational Corporations manage (Arcelik global) its subsidiaries. 3. To understand how Multinational Corporations (Arcelik global) communicate with international or global publics. Research Questions 1. The main global PR strategies employed by multinational corporations (Arcelik global) 2. How subsidiaries of multinational corporations like Arcelik Global are managed. 3. How multinational corporations, like Arcelik worldwide, interact with international publics.

Keywords: multinational corporation, ethnocentric model, polycentric model, international public relations

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Authors: Maryam Ghareh Chaei, Masuzyo Chilwesa, Ali Akbarnezhad, Arnaud Castel, Redmond Lloyd, Stephen Foster

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Cement hydration is an exothermic chemical reaction generally leading to a rise in concrete’s temperature. This internal heating of concrete may, in turn, lead to a temperature difference between the hotter interior and the cooler exterior of concrete and thus differential thermal stresses in early ages which could be particularly significant in mass concrete. Such differential thermal stresses result in early age thermal cracking of concrete when exceeding the concrete’s tensile strength. The extent of temperature rise and thus early age differential thermal stresses is generally a function of hydration heat intensity, thermal properties of concrete and size of the concrete element. Both hydration heat intensity and thermal properties of concrete may vary considerably with variations in the type cementitious materials and other constituents. With this in mind, partial replacement of cement with supplementary cementitious materials including fly ash and ground granulated blast furnace slag has been investigated widely as an effective strategy to moderate the heat generation rate and thus reduce the risk of early age thermal cracking of concrete. However, there is currently a lack of adequate literature on effect of partial replacement of cement with fly ash and/or ground granulated blast furnace slag on the thermal properties of concrete. This paper presents the results of an experimental conducted to evaluate the effect of addition of varying percentages of fly ash (up to 60%) and ground granulated blast furnace slag (up to 50%) on the heat capacity and thermal conductivity of early age cement paste. The water to cementitious materials ratio is kept 0.45 for all the paste samples. The results of the experimental studies were used in a numerical analysis performed using Comsol Multiphysics to highlight the effects of variations in the thermal properties of concrete, due to variations in the type of aggregate and content of supplemenraty cementitious materials, on the risk of early age cracking of a concrete raft.

Keywords: thermal diffusivity, early age thermal cracking, concrete, supplementary cementitious materials

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Authors: Sofia Nilsson, Alicia Ohlsson, Linda-Marie Lundqvist, Aida Alvinius, Peder Hyllengren, Gerry Larsson

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In irregular warfare contexts, military personnel are often presented with morally ambiguous situations where they are aware of the morally correct choice but may feel prevented to follow through with it due to organizational demands. Moral stress and/or injury can be the outcome of the individual’s experienced dissonance. These types of challenges put a large demand on the individual to manage their own emotions and the emotions of others, particularly in the case of a leader. Both the ability and inability for emotional regulation can result in different combinations of short and long term reactions after morally stressful events, which can be either positive or negative. Our study analyzed the combination of these reactions based upon the types of morally challenging events that were described by the subjects. 1)What institutionalized norms concerning emotion regulation are favorable in short-and long-term perspectives after a morally stressful event? 2)What individual emotion-focused coping strategies are favorable in short-and long-perspectives after a morally stressful? To address these questions, we conducted a quantitative study in military contexts in Sweden and Norway on upcoming or current military officers (n=331). We tested a theoretical model built upon a recently developed qualitative study. The data was analyzed using factor analysis, multiple regression analysis and subgroup analyses. The results indicated that an individual’s restriction of emotion in order to achieve an organizational goal, which results in emotional dissonance, can be an effective short term strategy for both the individual and the organization; however, it appears to be unfavorable in a long-term perspective which can result in negative reactions. Our results are intriguing because they showed an increased percentage of reported negative long term reactions (13%), which indicated PTSD-related symptoms in comparison to previous Swedish studies which indicated lower PTSD symptomology.

Keywords: emotion culture, emotion coping, emotion management, military

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Authors: Wang Yichen, Haruka Yamashita

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In recent years, in the field of sports, decision making such as member in the game and strategy of the game based on then analysis of the accumulated sports data are widely attempted. In fact, in the NBA basketball league where the world's highest level players gather, to win the games, teams analyze the data using various statistical techniques. However, it is difficult to analyze the game data for each play such as the ball tracking or motion of the players in the game, because the situation of the game changes rapidly, and the structure of the data should be complicated. Therefore, it is considered that the analysis method for real time game play data is proposed. In this research, we propose an analytical model for "determining the optimal lineup composition" using the real time play data, which is considered to be difficult for all coaches. In this study, because replacing the entire lineup is too complicated, and the actual question for the replacement of players is "whether or not the lineup should be changed", and “whether or not Small Ball lineup is adopted”. Therefore, we propose an analytical model for the optimal player selection problem based on Small Ball lineups. In basketball, we can accumulate scoring data for each play, which indicates a player's contribution to the game, and the scoring data can be considered as a time series data. In order to compare the importance of players in different situations and lineups, we combine RNN (Recurrent Neural Network) model, which can analyze time series data, and NN (Neural Network) model, which can analyze the situation on the field, to build the prediction model of score. This model is capable to identify the current optimal lineup for different situations. In this research, we collected all the data of accumulated data of NBA from 2019-2020. Then we apply the method to the actual basketball play data to verify the reliability of the proposed model.

Keywords: recurrent neural network, players lineup, basketball data, decision making model

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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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Authors: Suleyman Kizil, Tahsin Sogut, Khalid M. Khawar

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Genus Allium includes 600 to 750 species and most of these including Allium tuncelianum (Kollman) N. Ozhatay, B. Mathew & Siraneci; Syn; A. macrochaetum Boiss. and Hausskn. subsp. tuncelianum Kollman] or Tunceli garlic is endemic to Eastern Turkish Province of Tunceli and Munzur mountains. They are edible, bear attractive white-to-purple flowers and fertile black seeds with deep seed dormancy. This study aimed to break seed dormancy of Tunceli garlic and determine the conditions for induction of bulblets on these seeds and increase their diameter by culturing them on MS medium supplemented different strengths of KNO3. Tunceli garlic seeds were collected from field grown plants. They were germinated on MS medium with or without 20 g/l sucrose followed by their culture on 1 × 1900 mg/l, 2 × 1900 mg/l, 4 ×1900 mg/l and 6 × 1900 mg/l mg/l KNO3 supplemented with 20 g/l sucrose to increase bulb diameter. Improved seeds germination was noted on MS medium with and without sucrose but with variation compared to previous reports. The bulb development percentage on each of the sprouted seeds was not parallel to the percentage of seed germination. The results showed 34% and 28.5% bulb induction was noted on germinated seeds after 150 and 158 days on MS medium containing 20 g l-1 sucrose and no sucrose respectively showing a delay of 8 days on the latter compared to the former. The results emphatically noted role of cold stratification on agar solidified MS medium supplemented with sucrose to improve seed germination. The best increase in bulb diameter was noted on MS medium containing 1 × 1900 mg/l KNO3 after 178 days with bulblet diameter and bulblet weight of 0.54 cm and 0.048 g, respectively. Consequently, the bulbs induced on sucrose containing MS medium could be transferred to pots earlier. Increased (>1 × 1900 mg/l KNO3) strengths of KNO3 induced negative effect on growth and development of Tunceli garlic bulbs. The strategy of seed germination and bulblet induction reported in this study could be positively used for conservation of this endemic plant species.

Keywords: Tunceli garlic, seed, dormancy, bulblets, bulb growth

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