Search results for: cannabis for therapeutic purpose (CTP)
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 8795

Search results for: cannabis for therapeutic purpose (CTP)

8075 Effects of Pre-Task Activities on the Writing Performance of Second Language Learners

Authors: Wajiha Fatima

Abstract:

Based on Rod Ellis’s (2002) the methodology of task-based teaching, this study explored the effects of pre-task activities on the Job Application letter of 102 ESL students (who were female and undergraduate learners). For this purpose, students were divided among three groups (Group A, Group B, and Group C), kept in control and experimental settings as well. Pre-task phase motivates the learners to perform the actual task. Ellis reportedly discussed four pre-task phases: (1) performing a similar task; (2) providing a model; (3) non-task preparation activities and (4) strategic planning. They were taught through above given three pre-task activities. Accordingly, the learners in control setting were supposed to write without any teaching aid while learners in an experimental situation were provided three different pre-task activities in each group. In order to compare the scores of the pre-test and post-test of the three groups, sample paired t-test was utilized. The obtained results of the written job application by the female students revealed that pre-task activities improved their performance in writing. On the other hand, the comparison of the three pre-task activities revealed that 'providing a model' outperformed the other two activities. For this purpose, ANOVA was utilized.

Keywords: pre-task activities, second language learners, task based language teaching, writing

Procedia PDF Downloads 166
8074 Examining the Concept of Sustainability in the Scenery Architecture of Naqsh-e-Jahan Square

Authors: Mahmood Naghizadeh, Maryam Memarian, Hourshad Irvash

Abstract:

Following the rise in the world population and the upward growth of urbanization, the design, planning, and management of the site scenery for the purpose of presentation and expansion of sustainable site scenery has turned to be the greatest concern to experts. Since the fundamental principles of the site scenery change more and less haphazardly over time, sustainable site scenery can be viewed as an ideal goal because both sustainability and dynamism come into view in urban site scenery and it wouldn’t be designed according to a set of pre-determined principles. Sustainable site scenery, as the ongoing interaction between idealism and pragmatism with sustainability factors, is a dynamic phenomenon created by bringing cultural, historical, social and natural scenery together. Such an interaction is not to subdue other factors but to reinforce the aforementioned factors. The sustainable site scenery is a persistently occurring event not only has attenuated over time but has gained strength. The sustainability of a site scenery or an event over time depends on its site identity which grows out of its continuous association with the past. The sustainability of a site scene or an event in a time frame intertwined with the identity of the place from past to present. This past history supports the present and future of the scene. The result of such a supportive role is the sustainability of site scenery. Isfahan Naqsh-e-Jahan Square is one of the most outstanding squares in the world and the best embodiment of Iranian site scenery architecture. This square is an arena that brings people together and a dynamic city center comprising various urban and religious complexes, spaces and facilities and is considered as one of the most favorable traditional urban space of Iran. Such a place can illustrate many factors related to sustainable site scenery. One the other hand, there are still no specific principles concerning sustainability in the architecture of site scenery. Meanwhile, sustainability is recognized as a rather modern view in architecture. The purpose of this research is to identify factors involved in sustainability in general and to examine their effects on site scenery architecture in particular. Finally, these factors will be studied with taking Naqsh-e-Jahan Square into account. This research adopts an analytic-descriptive approach that has benefited from the review of literature available in library studies and the documents related to sustainability and site scenery architecture. The statistical population used for the purpose of this research includes square constructed during the Safavid dynasty and Naqsh-e-Jahan Square was picked out as the case study. The purpose of this paper is to come up with a rough definition of sustainable site scenery and demonstrate this concept by analyzing it and recognizing the social, economic and ecological aspects of this project.

Keywords: Naqsh-e-Jahan Square, site scenery architecture, sustainability, sustainable site scenery

Procedia PDF Downloads 303
8073 An Analysis of Instruction Checklist Based on Universal Design for Learning

Authors: Yong Wook Kim

Abstract:

The purpose of this study is to develop an instruction analysis checklist applicable to inclusive setting based on the Universal Design for Learning Guideline 2.0. To do this, two self-validation reviews, two expert validity reviews, and two usability evaluations were conducted based on the Universal Design for Learning Guideline 2.0. After validation and usability evaluation, a total of 36 items consisting of 4 items for each instruction was developed. In all questions, examples are presented for the purpose of reinforcing concrete. All the items were judged by the 3-point scale. The observation results were provided through a radial chart allowing SWOT analysis of the universal design for learning of teachers. The developed checklist provides a description of the principles and guidelines in the checklist itself as it requires a thorough understanding by the observer of the universal design for learning through prior education. Based on the results of the study, the instruction criteria, the specificity of the criteria, the number of questions, and the method of arrangement were discussed. As a future research, this study proposed the characteristics of application of universal design for learning for each subject, the comparison with the observation results through the self-report teaching tool, and the continual revision and supplementation of the lecture checklist.

Keywords: inclusion, universal design for learning, instruction analysis, instruction checklist

Procedia PDF Downloads 273
8072 Social Enterprise Strategies for Financial Sustainability in the Economic Literature

Authors: Adam Bereczk

Abstract:

Due to persistent socioeconomic problems regarding sustainability and labour market equilibrium in Europe, the subjects of social economy gained considerable academic attention recently. At the meantime, social enterprises pursuing the double bottom line criteria, struggling to find the proper management philosophies and strategies to make their social purpose business financially sustainable. Despite the strategic management literature was developed mainly on the bases of large corporations, in the past years, the interpretation of strategy concepts became a frequent topic in scientific discussions in the case of small and medium-sized enterprises also. The topic of strategic orientations is a good example of the trend. However, less is known about the case of social enterprises, despite the fact, the majority of them are small businesses engaged in real business activities. The main purpose of this work is to give a comprehensive summary of different perspectives regarding the interpretations of strategic orientations of social enterprises. The novelty of this work is it shows the previous outcomes and models of scholars from various fields of economic science who tried to intertwine the two spheres in different forms, methodize the findings and draw attention to the shortcomings.

Keywords: social enterprises, business sustainability, strategic orientations, literature review

Procedia PDF Downloads 270
8071 Vital Pulp Therapy: A Paradigm Shift in Treating Irreversible Pulpitis

Authors: Fadwa Chtioui

Abstract:

Vital Pulp Therapy (VPT) is nowadays challenging the deep-rooted dogma of root canal treatment, being the only therapeutic option for permanent teeth diagnosed with irreversible pulpitis or carious pulp exposure. Histologic and clinical research has shown that compromised dental pulp can be treated without the full removal or excavation of all healthy pulp, and the outcome of the partial or full pulpotomy followed by a Tricalcium-Silicate-based dressing seems to show promising results in maintaining pulp vitality and preserving affected teeth in the long term. By reviewing recent advances in the techniques of VPT and their clinical effectiveness and safety in permanent teeth with irreversible Pulpitis, this work provides a new understanding of pulp pathophysiology and defense mechanisms and will reform dental practitioners' decision-making in treating irreversible pulpits from root canal therapy to vital pulp therapy by taking advantage of the biological effects of Tricalcium Silicate materials.

Keywords: irreversible pulpitis, vital pulp therapy, pulpotomy, Tricalcium Silicate

Procedia PDF Downloads 54
8070 Immunoliposome-Mediated Drug Delivery to Plasmodium-Infected and Non-Infected Red Blood Cells as a Dual Therapeutic/Prophylactic Antimalarial Strategy

Authors: Ernest Moles, Patricia Urbán, María Belén Jiménez-Díaz, Sara Viera-Morilla, Iñigo Angulo-Barturen, Maria Antònia Busquets, Xavier Fernàndez-Busquets

Abstract:

Bearing in mind the absence of an effective vaccine against malaria and its severe clinical manifestations causing nearly half a million deaths every year, this disease represents nowadays a major threat to life. Besides, the basic rationale followed by currently marketed antimalarial approaches is based on the administration of drugs on their own, promoting the emergence of drug-resistant parasites owing to the limitation in delivering drug payloads into the parasitized erythrocyte high enough to kill the intracellular pathogen while minimizing the risk of causing toxic side effects to the patient. Such dichotomy has been successfully addressed through the specific delivery of immunoliposome (iLP)-encapsulated antimalarials to Plasmodium falciparum-infected red blood cells (pRBCs). Unfortunately, this strategy has not progressed towards clinical applications, whereas in vitro assays rarely reach drug efficacy improvements above 10-fold. Here, we show that encapsulation efficiencies reaching >96% can be achieved for the weakly basic drugs chloroquine (CQ) and primaquine using the pH gradient active loading method in liposomes composed of neutrally charged, saturated phospholipids. Targeting antibodies are best conjugated through their primary amino groups, adjusting chemical crosslinker concentration to retain significant antigen recognition. Antigens from non-parasitized RBCs have also been considered as targets for the intracellular delivery of drugs not affecting the erythrocytic metabolism. Using this strategy, we have obtained unprecedented nanocarrier targeting to early intraerythrocytic stages of the malaria parasite for which there is a lack of specific extracellular molecular tags. Polyethylene glycol-coated liposomes conjugated with monoclonal antibodies specific for the erythrocyte surface protein glycophorin A (anti-GPA iLP) were capable of targeting 100% RBCs and pRBCs at the low concentration of 0.5 μM total lipid in the culture, with >95% of added iLPs retained into the cells. When exposed for only 15 min to P. falciparum in vitro cultures synchronized at early stages, free CQ had no significant effect over parasite viability up to 200 nM drug, whereas iLP-encapsulated 50 nM CQ completely arrested its growth. Furthermore, when assayed in vivo in P. falciparum-infected humanized mice, anti-GPA iLPs cleared the pathogen below detectable levels at a CQ dose of 0.5 mg/kg. In comparison, free CQ administered at 1.75 mg/kg was, at most, 40-fold less efficient. Our data suggest that this significant improvement in drug antimalarial efficacy is in part due to a prophylactic effect of CQ found by the pathogen in its host cell right at the very moment of invasion.

Keywords: immunoliposomal nanoparticles, malaria, prophylactic-therapeutic polyvalent activity, targeted drug delivery

Procedia PDF Downloads 365
8069 Improved Approach to the Treatment of Resistant Breast Cancer

Authors: Lola T. Alimkhodjaeva, Lola T. Zakirova, Soniya S. Ziyavidenova

Abstract:

Background: Breast cancer (BC) is still one of the urgent oncology problems. The essential obstacle to the full anti-tumor therapy implementation is drug resistance development. Taking into account the fact that chemotherapy is main antitumor treatment in BC patients, the important task is to improve treatment results. Certain success in overcoming this situation has been associated with the use of methods of extracorporeal blood treatment (ECBT), plasmapheresis. Materials and Methods: We examined 129 women with resistant BC stages 3-4, aged between 56 to 62 years who had previously received 2 courses of CAF chemotherapy. All patients additionally underwent 2 courses of CAF chemotherapy but against the background ECBT with ultrasonic exposure. We studied the following parameters: 1. The highlights of peripheral blood before and after therapy. 2. The state of cellular immunity and identification of activation markers CD23 +, CD25 +, CD38 +, CD95 + on lymphocytes was performed using monoclonal antibodies. Evaluation of humoral immunity was determined by the level of main classes of immunoglobulins IgG, IgA, IgM in serum. 3. The degree of tumor regression was assessed by WHO recommended 4 gradations. (complete - 100%, partial - more than 50% of initial size, process stabilization–regression is less than 50% of initial size and tumor advance progressing). 4. Medical pathomorphism in the tumor was determined by Lavnikova. 5. The study of immediate and remote results, up to 3 years and more. Results and Discussion: After performing extracorporeal blood treatment anemia occurred in 38.9%, leukopenia in 36.8%, thrombocytopenia in 34.6%, hypolymphemia in 26.8%. Studies of immunoglobulin fractions in blood serum were able to establish a certain relationship between the classes of immunoglobulin A, G, M and their functions. The results showed that after treatment the values of main immunoglobulins in patients’ serum approximated to normal. Analysis of expression of activation markers CD25 + cells bearing receptors for IL-2 (IL-2Rα chain) and CD95 + lymphocytes that were mediated physiological apoptosis showed the tendency to increase, which apparently was due to activation of cellular immunity cytokines allocated by ultrasonic treatment. To carry out ECBT on the background of ultrasonic treatment improved the parameters of the immune system, which were expressed in stimulation of cellular immunity and correcting imbalances in humoral immunity. The key indicator of conducted treatment efficiency is the immediate result measured by the degree of tumor regression. After ECBT performance the complete regression was 10.3%, partial response - 55.5%, process stabilization - 34.5%, tumor advance progressing no observed. Morphological investigations of tumor determined therapeutic pathomorphism grade 2 in 15%, in 25% - grade 3 and therapeutic pathomorphism grade 4 in 60% of patients. One of the main criteria for the effect of conducted treatment is to study the remission terms in the postoperative period (up to 3 years or more). The remission terms up to 3 years with ECBT was 34.5%, 5-year survival was 54%. Carried out research suggests that a comprehensive study of immunological and clinical course of breast cancer allows the differentiated approach to the choice of methods for effective treatment.

Keywords: breast cancer, immunoglobulins, extracorporeal blood treatment, chemotherapy

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8068 Biomedical Countermeasures to Category a Biological Agents

Authors: Laura Cochrane

Abstract:

The United States Centers for Disease Control and Prevention has established three categories of biological agents based on their ease of spread and the severity of the disease they cause. Category A biological agents are the highest priority because of their high degree of morbidity and mortality, ease of dissemination, the potential to cause social disruption and panic, special requirements for public health preparedness, and past use as a biological weapon. Despite the threat of Category A biological agents, opportunities for medical intervention exist. This work summarizes public information, consolidated and reviewed across the situational usefulness and disease awareness to offer discussion to three specific Category A agents: anthrax (Bacillus anthracis), botulism (Clostridium botulinum toxin), and smallpox (variola major), and provides an overview on the management of medical countermeasures available to treat these three (3) different types of pathogens. The medical countermeasures are discussed in the setting of pre-exposure prophylaxis, post-exposure prophylaxis, and therapeutic treatments to provide a framework for requirements in public health preparedness.

Keywords: anthrax, botulism, smallpox, medical countermeasures

Procedia PDF Downloads 67
8067 Phenomenological Analysis on the Experience of Volunteer Activities in Pre-Medical School Students

Authors: S. J. Yune, K. H. Park

Abstract:

The purpose of this study was to understand the experiences of medical students in volunteer activities and to draw implications for medical education. For this purpose, the questionnaire and the reflection essay on the volunteer experience of 54 students in the first year and 57 students in the second year were analyzed and analyzed. As a result, the participation of the students in the volunteer activities was the highest in the first semester and once a month in the second grade. Activities were mostly through volunteer organizations. The essence of the volunteering activities experience revealed through reflection essays was 'I want to avoid with fear' and 'I feel far away' in the recognition before volunteering activities. In terms of knowledge after participating in volunteer activities, 'breaking eggs and getting to know the world' and 'intellectual growth through social experience' appeared. In terms of attitude, it revealed 'deep reflection on me and others', 'understanding of service life'. And in terms of behavior, 'Begin preparing for a life of service' appeared. The results of this study revealed that volunteering activities provide students with opportunities for growth and development. In order to obtain more meaningful results, consciousness education related to social service should be done in advance.

Keywords: volunteering activity, pre-medical school student, reflection essay, qualitative analysis

Procedia PDF Downloads 179
8066 Impact of Storytelling for Effective Marketing and Reputation Management of Heritage Tourism Destination with Special Reference to Haflong (Assam, India)

Authors: Rohit Sarin

Abstract:

This paper is an attempt to prove the impact of storytelling for effective marketing and maintaining the reputation of the destination for long run. This notable aspect of heritage tourism is cultural exchange among the various communities who visit our country India. Every destination has a life cycle like the product known as destination life cycle. India is considered to be the hub of cultural heritage tourism; its cultural heritage tourism can be traced back to several centuries. Heritage tourism has gained the popularity of global cuisine activity. The statistics of 2014 reveals 903 million International Tourist in heritage tourism destination is done to know the impact of storytelling for their visit to particulars heritage tourism destination. SWOT analysis of the destination is undertaken for the research purpose. A collection of data from the travel agency was taken who visited the heritage tourism destination and were asked to fill questionnaire for the research purpose to know the impact of storytelling for their visit to destination. A total of 100 respondents filled the questionnaire. Likert scale was used in the paper also highlighted the scope, advantage and disadvantage of storytelling for effective marketing and reputation management.

Keywords: destination life cycle, heritage tourism, random sampling, reputation management, storytelling

Procedia PDF Downloads 563
8065 Role of Feedbacks in Simulation-Based Learning

Authors: Usman Ghani

Abstract:

Feedback is a vital element for improving student learning in a simulation-based training as it guides and refines learning through scaffolding. A number of studies in literature have shown that students’ learning is enhanced when feedback is provided with personalized tutoring that offers specific guidance and adapts feedback to the learner in a one-to-one environment. Thus, emulating these adaptive aspects of human tutoring in simulation provides an effective methodology to train individuals. This paper presents the results of a study that investigated the effectiveness of automating different types of feedback techniques such as Knowledge-of-Correct-Response (KCR) and Answer-Until- Correct (AUC) in software simulation for learning basic information technology concepts. For the purpose of comparison, techniques like simulation with zero or no-feedback (NFB) and traditional hands-on (HON) learning environments are also examined. The paper presents the summary of findings based on quantitative analyses which reveal that the simulation based instructional strategies are at least as effective as hands-on teaching methodologies for the purpose of learning of IT concepts. The paper also compares the results of the study with the earlier studies and recommends strategies for using feedback mechanism to improve students’ learning in designing and simulation-based IT training.

Keywords: simulation, feedback, training, hands-on, labs

Procedia PDF Downloads 361
8064 Storytelling as a Pedagogical Tool to Learn English Language in Higher Education: Using Reflection and Experience to Improve Learning

Authors: Barzan Hadi Hama Karim

Abstract:

The purpose of this research study is to determine how educators, students at the university level are using storytelling to support the educational process. This study provides a general framework about educational uses of storytelling as a pedagogical too to learn English language in the higher education and describes the different perceptions of people (teachers and students) at different levels. A survey is used to collect responses from a group of educators and students in educational settings to determine how they are using storytelling for educational purposes. The results show the current situation of educational uses of storytelling and explore some of the benefits and challenges educators face in implementing storytelling in their institutions. The purpose of our research is to investigate the impact of storytelling as a pedagogical tool to learn English language in higher education and its academic achievements on ESL students. It highlights findings that address the following questions: (1) How has storytelling been approached historically? (2) Is storytelling beneficial for students in early grades at university? (3) To what extent do teacher and student prefer storytelling as a pedagogical tool to teach and learn English language in higher education?

Keywords: storytelling, teacher's beliefs, student’s beliefs, student’s academic achievement, narrative, pedagogy, ESL

Procedia PDF Downloads 389
8063 Joint Training Offer Selection and Course Timetabling Problems: Models and Algorithms

Authors: Gianpaolo Ghiani, Emanuela Guerriero, Emanuele Manni, Alessandro Romano

Abstract:

In this article, we deal with a variant of the classical course timetabling problem that has a practical application in many areas of education. In particular, in this paper we are interested in high schools remedial courses. The purpose of such courses is to provide under-prepared students with the skills necessary to succeed in their studies. In particular, a student might be under prepared in an entire course, or only in a part of it. The limited availability of funds, as well as the limited amount of time and teachers at disposal, often requires schools to choose which courses and/or which teaching units to activate. Thus, schools need to model the training offer and the related timetabling, with the goal of ensuring the highest possible teaching quality, by meeting the above-mentioned financial, time and resources constraints. Moreover, there are some prerequisites between the teaching units that must be satisfied. We first present a Mixed-Integer Programming (MIP) model to solve this problem to optimality. However, the presence of many peculiar constraints contributes inevitably in increasing the complexity of the mathematical model. Thus, solving it through a general purpose solver may be performed for small instances only, while solving real-life-sized instances of such model requires specific techniques or heuristic approaches. For this purpose, we also propose a heuristic approach, in which we make use of a fast constructive procedure to obtain a feasible solution. To assess our exact and heuristic approaches we perform extensive computational results on both real-life instances (obtained from a high school in Lecce, Italy) and randomly generated instances. Our tests show that the MIP model is never solved to optimality, with an average optimality gap of 57%. On the other hand, the heuristic algorithm is much faster (in about the 50% of the considered instances it converges in approximately half of the time limit) and in many cases allows achieving an improvement on the objective function value obtained by the MIP model. Such an improvement ranges between 18% and 66%.

Keywords: heuristic, MIP model, remedial course, school, timetabling

Procedia PDF Downloads 592
8062 Formal Asymptotic Stability Guarantees, Analysis, and Evaluation of Nonlinear Controlled Unmanned Aerial Vehicle for Trajectory Tracking

Authors: Soheib Fergani

Abstract:

This paper concerns with the formal asymptotic stability guarantees, analysis and evaluation of a nonlinear controlled unmanned aerial vehicles (uav) for trajectory tracking purpose. As the system has been recognised as an under-actuated non linear system, the control strategy has been oriented towards a hierarchical control. The dynamics of the system and the mission purpose make it mandatory to provide an absolute proof of the vehicle stability during the maneuvers. For this sake, this work establishes the complete theoretical proof for an implementable control oriented strategy that asymptotically stabilizes (GAS and LISS) the system and has never been provided in previous works. The considered model is reorganized into two partly decoupled sub-systems. The concidered control strategy is presented into two stages: the first sub-system is controlled by a nonlinear backstepping controller that generates the desired control inputs to stabilize the second sub-system. This methodology is then applied to a harware in the loop uav simulator (SiMoDrones) that reproduces the realistic behaviour of the uav in an indoor environment has been performed to show the efficiency of the proposed strategy.

Keywords: UAV application, trajectory tracking, backstepping, sliding mode control, input to state stability, stability evaluation

Procedia PDF Downloads 47
8061 First-Principles Modeling of Nanoparticle Magnetization, Chaining, and Motion

Authors: Pierce Radecki, Pulkit Malik, Bharath Ramaswamy, Ben Shapiro

Abstract:

The ability to effectively design and test magnetic nanoparticles for controlled movement has been an elusive goal in the design of these particles. Magnetic nanoparticles of various characteristics have been created for use towards therapeutic effects, however the challenge of designing for controlled movement remains unmet. A step towards design in this aspect is a first principles model that captures and predicts the behaviors of particles in a magnetic field. The model is governed by four forces acting on the particles, the magnetic gradient, the dipole-dipole forces, the steric forces, and the viscous drag force. The particles are multi-core or single core, and incorporate a preferred magnetization axis. Particles exhibit behaviors, such as chaining, in simulations that are similar to those witnessed through experimentation. Currently, experimental results are being compared to the modeling results for verification of the model, through the analysis of chaining behaviors. This modeling system will be used in designing magnetic nanoparticles for specific chaining and movement behaviors.

Keywords: controlled movement, modeling, magnetic nanoparticles, nanoparticle design

Procedia PDF Downloads 295
8060 Biochemical Changes in the Liver of Mice after Exposure to Different Doses of Diclofenac Sodium

Authors: Deepak Mohan, Sushma Sharma

Abstract:

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are a group of widely used drugs for the treatment of rheumatoid diseases and to relieve pain and inflammation due to their analgesic anti-pyretic and anti-inflammatory properties. The therapeutic and many of the toxic effects of NSAIDs result from reversible inhibition of enzymes in the cyclooxygenase (COX) group. In the present investigation the effect of the drug on the concentration of lipids, and on the activity of the enzymes i.e. acid and alkaline phosphatase, GOT, GPT and lipid peroxidase were studied. There was a significant enhancement in the activities of both acid and alkaline phosphatase after 21 days of treatment. Proportionate increase in the MDA contents was observed after different days of diclofenac treatment. Cellular damage in the liver resulted in decrease in the activity of both GOT (Glutamate oxaloacetate transaminase) and GPT (Glutamate pyruvate transaminase) in both low and high dose groups. Significant decrease in the liver contents was also observed in both dose groups.

Keywords: anti-inflammatory, cyclooxygenase, glutamate oxaloacetate transaminase, malondialdehyde

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8059 Evaluating Factors Impacting Functioning Management Control Systems Becoming Dysfunctional Beyond Intra-Organizational Boundaries

Authors: Martin Kartomo

Abstract:

Though Management Control Systems (MCS) research has evolved beyond intra-organizational boundaries, there is limited understanding of the impact of a functioning MCS being functional beyond intra-organizational boundaries. The purpose of this research is to investigate factors that have an impact on functioning management Control Systems (MCS)becoming (dys-)functional beyond its intra-organizational boundaries. To bridge the theoretical gap, a systematic literature review is conducted to identify inter-and extra-organizational factors that are purposely suggested or unintendingly mentioned by MCS researchers to evaluate functioning MCS becoming (dys-)functional. A conceptual map is rationalized and constructed from five contingent inter-and extra-organizational MCS frameworks illuminating under-investigated MSC research areas and allowing new research avenues based on academically known factors. A multiple case study followed by a co-researcher discussion group with the purpose of identifying academically unknown factors for evaluating MCS (dys-)functionality beyond its intra-organizational boundaries. The study's result will help bridge the gap between what academics know and not know of evaluating MCS being functional beyond intra-organizational boundaries with the opportunity to develop better, more complete theories. Furthermore, it will help organizations to evaluate the impact of their activities beyond intra-organizational boundaries.

Keywords: management control systems, management control systems evaluation, management controls, control system

Procedia PDF Downloads 167
8058 Person-Environment Fit (PE Fit): Evidence from Brazil

Authors: Jucelia Appio, Danielle Deimling De Carli, Bruno Henrique Rocha Fernandes, Nelson Natalino Frizon

Abstract:

The purpose of this paper is to investigate if there are positive and significant correlations between the dimensions of Person-Environment Fit (Person-Job, Person-Organization, Person-Group and Person-Supervisor) at the “Best Companies to Work for” in Brazil in 2017. For that, a quantitative approach was used with a descriptive method being defined as a research sample the "150 Best Companies to Work for", according to data base collected in 2017 and provided by Fundação Instituto of Administração (FIA) of the University of São Paulo (USP). About the data analysis procedures, asymmetry and kurtosis, factorial analysis, Kaiser-Meyer-Olkin (KMO) tests, Bartlett sphericity and Cronbach's alpha were used for the 69 research variables, and as a statistical technique for the purpose of analyzing the hypothesis, Pearson's correlation analysis was performed. As a main result, we highlight that there was a positive and significant correlation between the dimensions of Person-Environment Fit, corroborating the H1 hypothesis that there is a positive and significant correlation between Person-Job Fit, Person-Organization Fit, Person-Group Fit and Person-Supervisor Fit.

Keywords: Human Resource Management (HRM), Person-Environment Fit (PE), strategic people management, best companies to work for

Procedia PDF Downloads 134
8057 Empirical Evaluation of Game Components Based on Learning Theory: A Preliminary Study

Authors: Seoi Lee, Dongjoo Chin, Heewon Kim

Abstract:

Gamification refers to a technique that applies game elements to non-gaming elements, such as education and exercise, to make people more engaged in these behaviors. The purpose of this study was to identify effective elements in gamification for changing human behaviors. In order to accomplish this purpose, a survey based on learning theory was developed, especially for assessing antecedents and consequences of behaviors, and 8 popular and 8 unpopular games were selected for comparison. A total of 407 adult males and females were recruited via crowdsourcing Internet marketplace and completed the survey, which consisted of 19 questions for antecedent and 14 questions for consequences. Results showed no significant differences in consequence questions between popular and unpopular games. For antecedent questions, popular games are superior to unpopular games in character customization, play type selection, a sense of belonging, patch update cycle, and influence or dominance. This study is significant in that it reveals the elements of gamification based on learning theory. Future studies need to empirically validate whether these factors affect behavioral change.

Keywords: gamification, learning theory, antecedent, consequence, behavior change, behaviorism

Procedia PDF Downloads 213
8056 Study of the Late Phase of Core Degradation during Reflooding by Safety Injection System for VVER1000 with ASTECv2 Computer Code

Authors: Antoaneta Stefanova, Rositsa Gencheva, Pavlin Groudev

Abstract:

This paper presents the modeling approach in SBO sequence for VVER 1000 reactors and describes the reactor core behavior at late in-vessel phase in case of late reflooding by HPIS and gives preliminary results for the ASTECv2 validation. The work is focused on investigation of plant behavior during total loss of power and the operator actions. The main goal of these analyses is to assess the phenomena arising during the Station blackout (SBO) followed by primary side high pressure injection system (HPIS) reflooding of already damaged reactor core at very late ‘in-vessel’ phase. The purpose of the analysis is to define how the later HPIS switching on can delay the time of vessel failure or possibly avoid vessel failure. For this purpose has been simulated an SBO scenario with injection of cold water by a high pressure pump (HPP) in cold leg at different stages of core degradation. The times for HPP injection were chosen based on previously performed investigations.

Keywords: VVER, operator action validation, reflooding of overheated reactor core, ASTEC computer code

Procedia PDF Downloads 408
8055 Comprehensive Analysis of RNA m5C Regulator ALYREF as a Suppressive Factor of Anti-tumor Immune and a Potential Tumor Prognostic Marker in Pan-Cancer

Authors: Yujie Yuan, Yiyang Fan, Hong Fan

Abstract:

Objective: The RNA methylation recognition protein Aly/REF export factor (ALYREF) is considered one type of “reader” protein acting as a recognition protein of m5C, has been reported involved in several biological progresses including cancer initiation and progression. 5-methylcytosine (m5C) is a conserved and prevalent RNA modification in all species, as accumulating evidence suggests its role in the promotion of tumorigenesis. It has been claimed that ALYREF mediates nuclear export of mRNA with m5C modification and regulates biological effects of cancer cells. However, the systematical regulatory pathways of ALYREF in cancer tissues have not been clarified, yet. Methods: The expression level of ALYREF in pan-cancer and their normal tissues was compared through the data acquired from The Cancer Genome Atlas (TCGA). The University of Alabama at Birmingham Cancer data analysis Portal UALCAN was used to analyze the relationship between ALYREF and clinical pathological features. The relationship between the expression level of ALYREF and prognosis of pan-cancer, and the correlation genes of ALYREF were figured out by using Gene Expression Correlation Analysis database GEPIA. Immune related genes were obtained from TISIDB (an integrated repository portal for tumor-immune system interactions). Immune-related research was conducted by using Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) and TIMER. Results: Based on the data acquired from TCGA, ALYREF has an obviously higher-level expression in various types of cancers compared with relevant normal tissues excluding thyroid carcinoma and kidney chromophobe. The immunohistochemical images on The Human Protein Atlas showed that ALYREF can be detected in cytoplasm, membrane, but mainly located in nuclear. In addition, a higher expression level of ALYREF in tumor tissue generates a poor prognosis in majority of cancers. According to the above results, cancers with a higher expression level of ALYREF compared with normal tissues and a significant correlation between ALYREF and prognosis were selected for further analysis. By using TISIDB, we found that portion of ALYREF co-expression genes (such as BIRC5, H2AFZ, CCDC137, TK1, and PPM1G) with high Pearson correlation coefficient (PCC) were involved in anti-tumor immunity or affect resistance or sensitivity to T cell-mediated killing. Furthermore, based on the results acquired from GEPIA, there was significant correlation between ALYREF and PD-L1. It was exposed that there is a negative correlation between the expression level of ALYREF and ESTIMATE score. Conclusion: The present study indicated that ALYREF plays a vital and universal role in cancer initiation and progression of pan-cancer through regulating mitotic progression, DNA synthesis and metabolic process, and RNA processing. The correlation between ALYREF and PD-L1 implied ALYREF may affect the therapeutic effect of immunotherapy of tumor. More evidence revealed that ALYREF may play an important role in tumor immunomodulation. The correlation between ALYREF and immune cell infiltration level indicated that ALYREF can be a potential therapeutic target. Exploring the regulatory mechanism of ALYREF in tumor tissues may expose the reason for poor efficacy of immunotherapy and offer more directions of tumor treatment.

Keywords: ALYREF, pan-cancer, immunotherapy, PD-L1

Procedia PDF Downloads 62
8054 Development Of Diabetes Mellitus In Overweight People

Authors: Ashiraliyev SHavkat

Abstract:

Relevance of the topic: Diabetes mellitus in overweight people development and absence of treatment measures. Objective: to give patients the correct instructions on proper nutrition, to organize a network of preventive and therapeutic measures. Materials and methods: Multidisciplinary Tashkent Medical Academy. As a result of objective observations in patients who applied to the clinic, 28 11 overweight patients had to type 2 diabetes. Diabetesmellituswasdiagnosed. Results: 11.5 mmol / L on an empty stomach in the morning. EDT yes. Pathogenesis: fat content in the diet of patients with diabetes mellitus. Carbohydrate foods make up 60%. Eating disorders and physical inactivity As a result, the accumulation of glucose in the form of fat increases, and this is constantly in the blood, which led to an increase in the number of fatty acids. Clinic: Frequent fasting in 11 patients (hypothalamus). Associated with glucose deficiency), drinking 8-9 liters of water per day of blood in 7 people Systolic pressure 150 diastolic pressures 100. Sensation of ants in 3 people and poor eyesight in 5 people. Conclusion: Explain to patients that nutritional guidelines should be followed. Assign active movement in accordance with the energy entering the body.

Keywords: mellitus, diabetes, pathogenesis, clinic

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8053 Autophagy Promotes Vascular Smooth Muscle Cell Migration in vitro and in vivo

Authors: Changhan Ouyang, Zhonglin Xie

Abstract:

In response to proatherosclerotic factors such as oxidized lipids, or to therapeutic interventions such as angioplasty, stents, or bypass surgery, vascular smooth muscle cells (VSMCs) migrate from the media to the intima, resulting in intimal hyperplasia, restenosis, graft failure, or atherosclerosis. These proatherosclerotic factors also activate autophagy in VSMCs. However, the functional role of autophagy in vascular health and disease remains poorly understood. In the present study, we determined the role of autophagy in the regulation of VSMC migration. Autophagy activity in cultured human aortic smooth muscle cells (HASMCs) and mouse carotid arteries was measured by Western blot analysis of microtubule-associated protein 1 light chain 3 B (LC3B) and P62. The VSMC migration was determined by scratch wound assay and transwell migration assay. Ex vivo smooth muscle cell migration was determined using aortic ring assay. The in vivo SMC migration was examined by staining the carotid artery sections with smooth muscle alpha actin (alpha SMA) after carotid artery ligation. To examine the relationship between autophagy and neointimal hyperplasia, C57BL/6J mice were subjected to carotid artery ligation. Seven days after injury, protein levels of Atg5, Atg7, Beclin1, and LC3B drastically increased and remained higher in the injured arteries three weeks after the injury. In parallel with the activation of autophagy, vascular injury-induced neointimal hyperplasia as estimated by increased intima/media ratio. The en face staining of carotid artery showed that vascular injury enhanced alpha SMA staining in the intimal cells as compared with the sham operation. Treatment of HASMCs with platelet-derived growth factor (PDGF), one of the major factors for vascular remodeling in response to vascular injury, increased Atg7 and LC3 II protein levels and enhanced autophagosome formation. In addition, aortic ring assay demonstrated that PDGF treated aortic rings displayed an increase in neovessel formation compared with control rings. Whole mount staining for CD31 and alpha SMA in PDGF treated neovessels revealed that the neovessel structures were stained by alpha SMA but not CD31. In contrast, pharmacological and genetic suppression of autophagy inhibits VSMC migration. Especially, gene silencing of Atg7 inhibited VSMC migration induced by PDGF. Furthermore, three weeks after ligation, markedly decreased neointimal formation was found in mice treated with chloroquine, an inhibitor of autophagy. Quantitative morphometric analysis of the injured vessels revealed a marked reduction in the intima/media ratio in the mice treated with chloroquine. Conclusion: Autophagy activation increases VSMC migration while autophagy suppression inhibits VSMC migration. These findings suggest that autophagy suppression may be an important therapeutic strategy for atherosclerosis and intimal hyperplasia.

Keywords: autophagy, vascular smooth muscle cell, migration, neointimal formation

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8052 Design, Development and Characterization of Pioglitazone Transdermal Drug Delivery System

Authors: Dwarakanadha Reddy Peram, D. Swarnalatha, C. Gopinath

Abstract:

The main aim of this research work was to design and development characterization of Pioglitazone transdermal drug delivery system by using various polymers such as Olibanum with different concentration by solvent evaporation technique. The prepared formulations were evaluated for different physicochemical characteristics like thickness, folding endurance, drug content, percentage moisture absorption, percentage moisture loss, percentage elongation break test and weight uniformity. The diffusion studies were performed by using modified Franz diffusion cells. The result of dissolution studies shows that formulation, F3 (Olibanum with 50 mg) showed maximum release of 99.95 % in 12hrs, whereas F1 (Olibanum and EC backing membrane) showed minimum release of 93.65% in 12 hr. Based on the drug release and physicochemical values obtained the formulation F3 is considered as an optimized formulation which shows higher percentage of drug release of 99.95 % in 12 hr. The developed transdermal patches increase the therapeutic efficacy and reduced toxic effect of pioglitazone.

Keywords: pioglitazone, olibanum, transdermal drug delivery system, drug release percantage

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8051 Synthesis, Characterization and in vitro DNA Binding and Cleavage Studies of Cu(II)/Zn(II) Dipeptide Complexes

Authors: A. Jamsheera, F. Arjmand, D. K. Mohapatra

Abstract:

Small molecules binding to specific sites along DNA molecule are considered as potential chemotherapeutic agents. Their role as mediators of key biological functions and their unique intrinsic properties make them particularly attractive therapeutic agents. Keeping in view, novel dipeptide complexes Cu(II)-Val-Pro (1), Zn(II)-Val-Pro (2), Cu(II)-Ala-Pro (3) and Zn(II)-Ala-Pro (4) were synthesized and thoroughly characterized using different spectroscopic techniques including elemental analyses, IR, NMR, ESI–MS and molar conductance measurements. The solution stability study carried out by UV–vis absorption titration over a broad range of pH proved the stability of the complexes in solution. In vitro DNA binding studies of complexes 1–4 carried out employing absorption, fluorescence, circular dichroism and viscometric studies revealed the binding of complexes to DNA via groove binding. UV–vis titrations of 1–4 with mononucleotides of interest viz., 5´-GMP and 5´-TMP were also carried out. The DNA cleavage activity of the complexes 1 and 2 were ascertained by gel electrophoresis assay which revealed that the complexes are good DNA cleavage agents and the cleavage mechanism involved a hydrolytic pathway. Furthermore, in vitro antitumor activity of complex 1 was screened against human cancer cell lines of different histological origin.

Keywords: dipeptide Cu(II) and Zn(II) complexes, DNA binding profile, pBR322 DNA cleavage, in vitro anticancer activity

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8050 An Investigation into the Effects of Anxiety Sensitivity in Adolescents on Anxiety Disorder and Childhood Depression

Authors: Ismail Seçer

Abstract:

The purpose of this study is to investigate the effects of anxiety sensitivity in adolescents on anxiety disorder and childhood depression. Mood disorders and anxiety disorders in children and adolescents can be given examples of important research topics in recent years. The participants of the study consist of 670 students in Erzurum and Erzincan city centers. The participants of the study were 670 secondary and high school students studying in city centers of Erzurum and Erzincan. The participants were chosen based on convenience sampling. The participants were between the ages of 13 and 18 (M=15.7, Ss= 1.35) and 355 were male and 315 were female. The data were collected through Anxiety Sensitivity Index and Anxiety and Depression Index for Children and Adolescents. For data analysis, Correlation analysis and Structural Equation Model were used. In this study, correlational descriptive survey was used. This model enables the researcher to make predictions related to different variables based on the information obtained from one or more variables. Therefore, the purpose is to make predictions considering anxiety disorder and childhood depression based on anxiety sensitivity. For this purpose, latent variable and structural equation model was used. Structural equation model is an analysis method which enables the identification of direct and indirect effects by determining the relationship between observable and latent variables and testing their effects on a single model. CFI, RMR, RMSEA and SRMR, which are commonly accepted fit indices in structural equation model, were used. The results revealed that anxiety sensitivity impacts anxiety disorder and childhood depression through direct and indirect effects in a positive way. The results are discussed in line with the relevant literature. This finding can be considered that anxiety sensitivity can be a significant risk source in terms of children's and adolescents’ anxiety disorder experience. This finding is consistent with relevant research highlighting that in case the anxiety sensitivity increases then the obsessive compulsive disorder and panic attack increase too. The adolescents’ experience of anxiety can be attributed to anxiety sensitivity.

Keywords: anxiety sensitivity, anxiety, depression, structural equation

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8049 Profiling of the Cell-Cycle Related Genes in Response to Efavirenz, a Non-Nucleoside Reverse Transcriptase Inhibitor in Human Lung Cancer

Authors: Rahaba Marima, Clement Penny

Abstract:

The Health-related quality of life (HRQoL) for HIV positive patients has improved since the introduction of the highly active antiretroviral treatment (HAART). However, in the present HAART era, HIV co-morbidities such as lung cancer, a non-AIDS (NAIDS) defining cancer have been documented to be on the rise. Under normal physiological conditions, cells grow, repair and proliferate through the cell-cycle as cellular homeostasis is important in the maintenance and proper regulation of tissues and organs. Contrarily, the deregulation of the cell-cycle is a hallmark of cancer, including lung cancer. The association between lung cancer and the use of HAART components such as Efavirenz (EFV) is poorly understood. This study aimed at elucidating the effects of EFV on the cell-cycle genes’ expression in lung cancer. For this purpose, the human cell-cycle gene array composed of 84 genes was evaluated on both normal lung fibroblasts (MRC-5) cells and adenocarcinoma (A549) lung cells, in response to 13µM EFV or 0.01% vehicle. The ±2 up or down fold change was used as a basis of target selection, with p < 0.05. Additionally, RT-qPCR was done to validate the gene array results. Next, In-silico bio-informatics tools, Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), Reactome, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Ingenuity Pathway Analysis (IPA) were used for gene/gene interaction studies as well as to map the molecular and biological pathways influenced by the identified targets. Interestingly, the DNA damage response (DDR) pathway genes such as p53, Ataxia telangiectasia mutated and Rad3 related (ATR), Growth arrest and DNA damage inducible alpha (GADD45A), HUS1 checkpoint homolog (HUS1) and Role of radiation (RAD) genes were shown to be upregulated following EFV treatment, as revealed by STRING analysis. Additionally, functional enrichment analysis by the KEGG pathway revealed that most of the differentially expressed gene targets function at the cell-cycle checkpoint such as p21, Aurora kinase B (AURKB) and Mitotic Arrest Deficient-Like 2 (MAD2L2). Core analysis by IPA revealed that p53 downstream targets such as survivin, Bcl2, and cyclin/cyclin dependent kinases (CDKs) complexes are down-regulated, following exposure to EFV. Furthermore, Reactome analysis showed a significant increase in cellular response to stress genes, DNA repair genes, and apoptosis genes, as observed in both normal and cancerous cells. These findings implicate the genotoxic effects of EFV on lung cells, provoking the DDR pathway. Notably, the constitutive expression of this pathway (DDR) often leads to uncontrolled cell proliferation and eventually tumourigenesis, which could be the attribute of HAART components’ (such as EFV) effect on human cancers. Targeting the cell-cycle and its regulation holds a promising therapeutic intervention to the potential HAART associated carcinogenesis, particularly lung cancer.

Keywords: cell-cycle, DNA damage response, Efavirenz, lung cancer

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8048 Osteosuture in Fixation of Displaced Lateral Third Clavicle Fractures: A Case Report

Authors: Patrícia Pires, Renata Vaz, Bárbara Teles, Marco Pato, Pedro Beckert

Abstract:

Introduction: The management of lateral third clavicle fractures can be challenging due to difficulty in distinguishing subtle variations in the fracture pattern, which may be suggestive of potential fracture instability. They occur most often in men between 30 and 50 years of age, and in individuals over 70 years of age, its distribution is equal between both men and women. These fractures account for 10%–30% of all clavicle fractures and roughly 30%–45% of all clavicle nonunion fractures. Lateral third clavicle fractures may be treated conservatively or surgically, and there is no gold standard, although the risk of nonunion or pseudoarthrosis impacts the recommendation of surgical treatment when these fractures are unstable. There are many strategies for surgical treatment, including locking plates, hook plates fixation, coracoclavicular fixation using suture anchors, devices or screws, tension band fixation with suture or wire, transacromial Kirschner wire fixation and arthroscopically assisted techniques. Whenever taking the hardware into consideration, we must not disregard that obtaining adequate lateral fixation of small fragments is a difficult task, and plates are more associated to local irritation. The aim of the appropriate treatment is to ensure fracture healing and a rapid return to preinjury activities of daily living but, as explained, definitive treatment strategies have not been established and the variety of techniques avalilable add up to the discussion of this topic. Methods and Results: We present a clinical case of a 43-year-old man with the diagnosis of a lateral third clavicle fracture (Neer IIC) in the sequence of a fall on his right shoulder after a bicycle fall. He was operated three days after the injury, and through K-wire temporary fixation and indirect reduction using a ZipTight, he underwent osteosynthesis with an interfragmentary figure-of-eight tension band with polydioxanone suture (PDS). Two weeks later, there was a good aligment. He kept the sling until 6 weeks pos-op, avoiding efforts. At 7-weeks pos-op, there was still a good aligment, starting the physiotherapy exercises. After 10 months, he had no limitation in mobility or pain and returned to work with complete recovery in strength. Conclusion: Some distal clavicle fractures may be conservatively treated, but it is widely accepted that unstable fractures require surgical treatment to obtain superior clinical outcomes. In the clinical case presented, the authors chose an osteosuture technique due to the fracture pattern, its location. Since there isn´t a consensus on the prefered fixation method, it is important for surgeons to be skilled in various techniques and decide with their patient which approach is most appropriate for them, weighting the risk-benefit of each method. For instance, with the suture technique used, there is no wire migration or breakage, and it doesn´t require a reoperation for hardware removal; there is also less tissue exposure since it requires a smaller approach in comparison to the plate fixation and avoids cuff tears like the hook plate. The good clinical outcome on this case report serves the purpose of expanding the consideration of this method has a therapeutic option.

Keywords: lateral third, clavicle, suture, fixation

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8047 Partnering With Key Stakeholders for Successful Implementation of Inhaled Analgesia for Specific Emergency Department Presentations

Authors: Sarah Hazelwood, Janice Hay

Abstract:

Methoxyflurane is an inhaled analgesic administered via a disposable inhaler, which has been used in Australia for 40 years for the management of pain in children & adults. However, there is a lack of data for methoxyflurane as a frontline analgesic medication within the emergency department (ED). This study will investigate the usefulness of methoxyflurane in a private inner-city ED. The study concluded that the inclusion of all key stakeholders in the prescribing, administering & use of this new process led to comprehensive uptake & vastly positive outcomes for consumer & health professionals. Method: A 12-week prospective pilot study was completed utilizing patients presenting to the ED in pain (numeric pain rating score > 4) that fit the requirement of methoxyflurane use (as outlined in the Australian Prescriber information package). Nurses completed a formatted spreadsheet for each interaction where methoxyflurane was used. Patient demographics, day, time, initial numeric pain score, analgesic response time, the reason for use, staff concern (free text), & patient feedback (free text), & discharge time was documented. When clinical concern was raised, the researcher retrieved & reviewed patient notes. Results: 140 methoxyflurane inhalers were used. 60% of patients were 31 years of age & over (n=82) with 16% aged 70+. The gender split; 51% male: 49% female. Trauma-related pain (57%) saw the highest use of administration, with the evening hours (1500-2259) seeing the greatest numbers used (39%). Tuesday, Thursday & Sunday shared the highest daily use throughout the study. A minimum numerical pain score of 4/10 (n=13, 9%), with the ranges of 5 - 7/10 (moderate pain) being given by almost 50% of patients. Only 3 instances of pain scores increased post use of methoxyflurane (all other entries showed pain score < initial rating). Patients & staff noted obvious analgesic response within 3 minutes (n= 96, 81%, of administration). Nurses documented a change in patient vital signs for 4 of the 15 patient-related concerns; the remaining concerns were due to “gagging” on the taste, or “having a coughing episode”; one patient tried to leave the department before the procedure was attended (very euphoric state). Upon review of the staff concerns – no adverse events occurred & return to therapeutic vitals occurred within 10 minutes. Length of stay for patients was compared with similar presentations (such as dislocated shoulder or ankle fracture) & saw an average 40-minute decrease in time to discharge. Methoxyflurane treatment was rated “positively” by > 80% of patients – with remaining feedback related to mild & transient concerns. Staff similarly noted a positive response to methoxyflurane as an analgesic & as an added tool for frontline analgesic purposes. Conclusion: Methoxyflurane should be used on suitable patient presentations requiring immediate, short term pain relief. As a highly portable, non-narcotic avenue to treat pain this study showed obvious therapeutic benefit, positive feedback, & a shorter length of stay in the ED. By partnering with key stake holders, this study determined methoxyflurane use decreased work load, decreased wait time to analgesia, and increased patient satisfaction.

Keywords: analgesia, benefits, emergency, methoxyflurane

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8046 Cancer Stem Cell-Associated Serum Proteins Obtained by Maldi TOF/TOF Mass Spectrometry in Women with Triple-Negative Breast Cancer

Authors: Javier Enciso-Benavides, Fredy Fabian, Carlos Castaneda, Luis Alfaro, Alex Choque, Aparicio Aguilar, Javier Enciso

Abstract:

Background: The use of biomarkers in breast cancer diagnosis, therapy, and prognosis has gained increasing interest. Cancer stem cells (CSCs) are a subpopulation of tumor cells that can drive tumor initiation and may cause relapse. Therefore, due to the importance of diagnosis, therapy, and prognosis, several biomarkers that characterize CSCs have been identified; however, in treatment-naïve triple-negative breast tumors, there is an urgent need to identify new biomarkers and therapeutic targets. According to this, the aim of this study was to identify serum proteins associated with cancer stem cells and pluripotency in women with triple-negative breast tumors in order to subsequently identify a biomarker for this type of breast tumor. Material and Methods: Whole blood samples from 12 women with histopathologically diagnosed triple-negative breast tumors were used after obtaining informed consent from the patient. Blood serum was obtained by conventional procedure and frozen at -80ºC. Identification of cancer stem cell-associated proteins was performed by matrix-assisted laser desorption/ionisation-assisted laser desorption/ionisation mass spectrometry (MALDI-TOF MS), protein analysis was obtained using the AB Sciex TOF/TOF™ 5800 system (AB Sciex, USA). Sequences not aligned by ProteinPilot™ software were analyzed by Protein BLAST. Results: The following proteins related to pluripotency and cancer stem cells were identified by MALDI TOF/TOF mass spectrometry: A-chain, Serpin A12 [Homo sapiens], AIEBP [Homo sapiens], Alpha-one antitrypsin, AT {internal fragment} [human, partial peptide, 20 aa] [Homo sapiens], collagen alpha 1 chain precursor variant [Homo sapiens], retinoblastoma-associated protein variant [Homo sapiens], insulin receptor, CRA_c isoform [Homo sapiens], Hydroxyisourate hydrolase [Streptomyces scopuliridis], MUCIN-6 [Macaca mulatta], Alpha-actinin-3 [Chrysochloris asiatica], Polyprotein M, CRA_d isoform, partial [Homo sapiens], Transcription factor SOX-12 [Homo sapiens]. Recommendations: The serum proteins identified in this study should be investigated in the exosome of triple-negative breast cancer stem cells and in the blood serum of women without breast cancer. Subsequently, proteins found only in the blood serum of women with triple-negative breast cancer should be identified in situ in triple-negative breast cancer tissue in order to identify a biomarker to study the evolution of this type of cancer, or that could be a therapeutic target. Conclusions: Eleven cancer stem cell-related serum proteins were identified in 12 women with triple-negative breast cancer, of which MUCIN-6, retinoblastoma-associated protein variant, transcription factor SOX-12, and collagen alpha 1 chain are the most representative and have not been studied so far in this type of breast tumor. Acknowledgement: This work was supported by Proyecto CONCYTEC–Banco Mundial “Mejoramiento y Ampliacion de los Servicios del Sistema Nacional de Ciencia Tecnología e Innovacion Tecnologica” 8682-PE (104-2018-FONDECYT-BM-IADT-AV).

Keywords: triple-negative breast cancer, MALDI TOF/TOF MS, serum proteins, cancer stem cells

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