Search results for: Uputaua therapeutic approach

Authors: Ila Gupta

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The government hospitals in India by and large lack the necessary aesthetic therapeutic components, both in their interior and exterior space designs. These components especially in terms of color application are important to the emotional as well as physical well being of the patients and other participants of the space. The preliminary survey of few government hospitals in Uttarakhand, India, reveals that the government health care industry provides a wide scope for intervention. All most all of the spaces do not adhere to a proper therapeutic color scheme which directly helps the well-being of their patients and workers. The paper aims to conduct a survey and come up with recommendations in this regard. The government hospitals also lack a proper signage system which allows the space to be more user-friendly. The hospital spaces in totality also have scope for improvement in terms of space/landscape design which enhances the work environment in an efficient and positive way. This study will thus enable to come up with feasible recommendations for healthcare and built environment as well as retrofitting the existing spaces. The objective of the paper is mainly on few case studies. The present ambience in many government hospitals generally lacks a welcoming ambience. It is proposed to select one or two government hospitals and demonstrate application of appropriate and self-sustainable color schemes, placement of artifacts, changes in outdoor and indoor space design to bring about a change that is conducive for cognitive healing. Exterior changes to existing and old hospital buildings in depressed historic areas signify financial investment and change, and have the potential to play a significant role in both urban preservation and revitalization. Changes to exterior architectural colors are perhaps the most visible signifier of such revitalization, as the use of color changes as a tool in façade and interior improvement programs. The present project will provide its recommendations on the basis of case studies done in the Indian Public Health Care system. Furthermore, the recommendations will be in accordance with the extended study conducted in Indian Ayurvedic, Yogic texts as well as Vastu texts, which provides knowledge about built environments and healing properties of color.

Keywords: color, environment, facade, architectural color history, interior improvement programs, community development, district/government hospitals

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Authors: Hamidreza Akbari

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In this paper, for detection of inclined eccentricity in an induction motor, time–frequency analysis of the stator startup current is carried out. For this purpose, the discrete wavelet transform is used. Data are obtained from simulations, using winding function approach. The results show the validity of the approach for detecting the fault and discriminating with respect to other faults.

Keywords: induction machine, fault, DWT, electric

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Authors: Jana Tchekalarova, Milena Atanasova, Katerina Georgieva

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Melatonin deficit can cause a disturbance in emotional status and circadian rhythms of the endocrine system in the body. Both pharmacological and alternative approaches are applied for correction of dysfunctions driven by changes in circadian dynamics of many physiological indicators. In the present study, we tested and compare the beneficial effect of agomelatine (40 mg/kg, i.p. for 3 weeks) and endurance training on depressive behavior in two models of melatonin deficit in rat. The role of disturbed circadian rhythms of plasma melatonin and corticosterone secretion in the mechanism of these treatments was also explored. The continuous exercise program attenuated depressive responses associated with disrupted diurnal rhythm of home-cage motor activity, anhedonia in the sucrose preference test, and despair-like behavior in the forced swimming test were attenuated by agomelatine exposed to chronic constant light (CCL) and long-term exercise in pinealectomized rats. Parallel to the observed positive effect on the emotional status, agomelatine restored CCL-induced impairment of circadian patterns of plasma melatonin but not that of corticosterone. In opposite, exercise training diminished total plasma corticosterone levels and corrected its flattened pattern while it was unable to correct melatonin deficit in pinealectomy. These results suggest that the antidepressant-like effect of pharmacological and alternative approach might be mediated via two different mechanism, correction of the disturbed circadian rhythm of melatonin and corticosterone, respectively. Therefore, these treatment approaches might have a potential therapeutic application in different subpopulations of people characterized by a melatonin deficiency. This work was supported by the National Science Fund of Bulgaria (research grant # № DN 03/10; DN# 12/6).

Keywords: agomelatine, exercise training, melatonin deficit, corticosterone

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Authors: Ola A. Younis, Said Ghoul

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Systems running these days are huge, complex and exist in many versions. Controlling these versions and tracking their changes became a very hard process as some versions are created using meaningless names or specifications. Many versions of a system are created with no clear difference between them. This leads to mismatching between a user’s request and the version he gets. In this paper, we present a system versions meta-modeling approach that produces versions based on system’s features. This model reduced the number of steps needed to configure a release and gave each version its unique specifications. This approach is applicable for systems that use features in its specification.

Keywords: features, meta-modeling, semantic modeling, SPL, VCS, versioning

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Authors: Ghada Badr, Manar Hosny, Nuha Bintayyash, Eman Albilali, Souad Larabi Marie-Sainte

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The median problem is significantly applied to derive the most reasonable rearrangement phylogenetic tree for many species. More specifically, the problem is concerned with finding a permutation that minimizes the sum of distances between itself and a set of three signed permutations. Genomes with equal number of genes but different order can be represented as permutations. In this paper, an algorithm, namely BeamGA median, is proposed that combines a heuristic search approach (local beam) as an initialization step to generate a number of solutions, and then a Genetic Algorithm (GA) is applied in order to refine the solutions, aiming to achieve a better median with the smallest possible reversal distance from the three original permutations. In this approach, any genome rearrangement distance can be applied. In this paper, we use the reversal distance. To the best of our knowledge, the proposed approach was not applied before for solving the median problem. Our approach considers true biological evolution scenario by applying the concept of common intervals during the GA optimization process. This allows us to imitate a true biological behavior and enhance genetic approach time convergence. We were able to handle permutations with a large number of genes, within an acceptable time performance and with same or better accuracy as compared to existing algorithms.

Keywords: median problem, phylogenetic tree, permutation, genetic algorithm, beam search, genome rearrangement distance

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Authors: Shahzad Karim Bhatti

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Background: Ozone is a combination of oxygen and can be used in treatment of low back pain due to herniated disc. It is a minimally invasive procedure using biochemical properties of ozone resulting in reduced volume of disc and inflammation resulting in significant pain relief. Aim: The purpose of this study was to evaluate the effectiveness of ozone therapy in combination with peri-ganglionic injection of local anesthetic and corticosteroid. Material and Methods: This retrospective study was done at the Interventional Radiology Department of Mayo Hospital, Lahore. A total of 49000 patients were included from January 2008 to March 2022. All the patients presented with clinical signs and symptoms of lumber disc herniation, which was confirmed by a MRI scan of the lumbar sacral spine. The pain reduction was calculated using modified MacNab method. All the patients underwent percutaneous injection of ozone at a concentration of 27 micrograms/ml to lumber disc under fluoroscopic guidance with combination of local anesthetic and corticosteroid in peri-ganglionic space. Results were evaluated by two expert observers who were blinded to patient treatment. Results A satisfactory therapeutic outcome was obtained. 55% of the patients showed complete recovery with resolution of symptoms. 20% of the patients complained of occasional episodic pain with no limitation of occupational activity. 15% of cases showed insufficient improvement. 5% of cases had insufficient improvement and went for surgery. 10% of cases never turned up after the first visit. Conclusion Intradiscal ozone for the treatment of herniated discs has revolutionized percutaneous approach to nerve root compression making it safer, economical and easier to repeat without any side effects than treatments currently used in Pakistan.

Keywords: pain, prolapse, Ozone, backpain

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Authors: Sie Long Kek, Wah June Leong, Kok Lay Teo

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Linear quadratic Gaussian model is a standard mathematical model for the stochastic optimal control problem. The combination of the linear quadratic estimation and the linear quadratic regulator allows the state estimation and the optimal control policy to be designed separately. This is known as the separation principle. In this paper, an efficient computational method is proposed to solve the linear quadratic Gaussian problem. In our approach, the Hamiltonian function is defined, and the necessary conditions are derived. In addition to this, the output error is defined and the least-square optimization problem is introduced. By determining the first-order necessary condition, the gradient of the sum squares of output error is established. On this point of view, the stochastic approximation approach is employed such that the optimal control policy is updated. Within a given tolerance, the iteration procedure would be stopped and the optimal solution of the linear-quadratic Gaussian problem is obtained. For illustration, an example of the linear-quadratic Gaussian problem is studied. The result shows the efficiency of the approach proposed. In conclusion, the applicability of the approach proposed for solving the linear quadratic Gaussian problem is highly demonstrated.

Keywords: iteration procedure, least squares solution, linear quadratic Gaussian, output error, stochastic approximation

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Authors: Adewoyin O. Olusegun, Emmanuel O. Joshua, Marvel L. Akinyemi

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The heterogeneous nature of the subsurface requires the use of factual information to deal with rather than assumptions or generalized equations. Therefore, there is need to determine the actual rate of settlement possible in the soil before structures are built on it. This information will help in determining the type of foundation design and the kind of reinforcement that will be necessary in constructions. This paper presents a simplified and a faster approach for determining foundation settlement in any type of soil using real field data acquired from seismic refraction techniques and cone penetration tests. This approach was also able to determine the depth of settlement of each strata of soil. The results obtained revealed the different settlement time and depth of settlement possible.

Keywords: heterogeneous, settlement, foundation, seismic, technique

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Authors: Hamesh Babu Nanvala, Madhuri Malhal Rao

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The overall development of the Institution is dependent on the approach and attitude of the principal. Influence of principal’s professionalism on overall development of the Institution is the aim of this paper. Professionalism means conducting oneself with responsibility, integrity, accountability and excellence. The predominant characteristic of professionalism is the temperament of oneself to work in the public interest. By summarizing the observations based on authors’ experience regarding professionalism of principals towards the development of their respective institutions and correlating these observations with the findings in the literature and opinion of other principals and staff, the authors conceived a conceptual approach with its attributes by practicing suggested approach principals that can achieve overall development of their institutions.

Keywords: achiever, development, institution, principal, professionalism, student, teacher

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Authors: Emmanuel Iyamuremye, Irenee Ndayambaje

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This study investigated the influence of Concrete Pictorial Abstract (CPA) teaching approach on mathematics achievement based on a sample of eighth-grade students (N = 10,345) from the Rwandan Lower Secondary School quasi-experimental study with pre-test and post-test control group of 2019 (RLSQES19). Key aspects studied included mathematics concept understanding and mathematics concept retention and how these are influenced by teacher's teaching approach. Specifically, the study aimed to a.) investigate students' concept understanding and concept retention in mathematics when exposed to CPA approach and to those exposed to non-CPA approach before and after the intervention, and b.) ascertain the significant difference between the performance of the students exposed to CPA approach and those exposed to non-CPA approach in terms of post-test scores and retention test scores. Two groups (control and experimental) undergone pre-test, post-test, and retention test. The assignment of control and experimental group among senior two classes from 10 schools was done randomly. The materials used to determine the performance of the students is a teacher-made test. Descriptive statistics and ANCOVA were used for the analysis of the study. For determining the improvement in concept understanding of mathematics, Hakes methods of calculating gain were used to analyze the pre-test and post test score. The level of performance of the two groups in the pre-test is below average level. During the post-test and retention test, the performance of students in non-CPA group is on average level, and students in CPA group are on above average level. Hakes methods of calculating gain revealed higher significant performance in the post-test and retention test of CPA group of students than non-CPA group of students.

Keywords: concept understanding, concept retention, performance, teaching approach

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Authors: Rasha Alshaye

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Blended learning has become an innovative model that combines face-to-face with e-learning approaches. The Saudi Electronic University (SEU) has adopted blended learning as a flexible approach that provides instructors and learners with a motivating learning environment to stimulate the teaching and learning process. This study investigates the perceptions of English language instructors, teaching the four English language skills at Saudi Electronic University. Four main domains were examined in this study; challenges that the instructors encounter while implementing the blended learning approach, enhancing student-instructor interaction, flexibility in teaching, and the lack of technical skills. Furthermore, the study identifies and represents the instructors’ aspirations and plans to utilize this approach in enhancing the teaching and learning experience. Main findings indicate that instructors at Saudi Electronic University experience some challenges while teaching the four language skills. However, they find the blended learning approach motivating and flexible for them and their students. This study offers some important understandings into how instructors are applying the blended learning approach and how this process can be enriched.

Keywords: blended learning, English language skills, English teaching, instructors' perceptions

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Authors: Yogesh Rai, Saurabh Singh, Sanjay Pandey, Dhananjay K. Sah, B. G. Roy, B. S. Dwarakanath, Anant N. Bhatt

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One of the most common signatures of highly malignant gliomas is their capacity to metabolize more glucose to lactic acid than normal brain tissues, even under normoxic conditions (Warburg effect), indicating that aerobic glycolysis is constitutively upregulated through stable genetic or epigenetic changes. However, oxidative phosphorylation (OxPhos) is also required to maintain the mitochondrial membrane potential for tumor cell survival. In the process of tumorigenesis, tumor cells during fastest growth rate exhibit both high glycolytic and high OxPhos. Therefore, metabolically reprogrammed cancer cells with combination of both aerobic glycolysis and altered OxPhos develop a robust metabolic phenotype, which confers a selective growth advantage. In our study, we grew the high glycolytic BMG-1 (glioma) cells with continuous exposure of mitochondrial uncoupler 2, 4, dinitro phenol (DNP) for 10 passages to obtain a phenotype of high glycolysis with enhanced altered OxPhos. We found that OxPhos modified BMG (OPMBMG) cells has similar growth rate and cell cycle distribution but high mitochondrial mass and functional enzymatic activity than parental cells. In in-vitro studies, OPMBMG cells showed enhanced invasion, proliferation and migration properties. Moreover, it also showed enhanced angiogenesis in matrigel plug assay. Xenografted tumors from OPMBMG cells showed reduced latent period, faster growth rate and nearly five folds reduction in the tumor take in nude mice compared to BMG-1 cells, suggesting that robust metabolic phenotype facilitates tumor formation and growth. OPMBMG cells which were found radio-resistant, showed enhanced radio-sensitization by 2-DG as compared to the parental BMG-1 cells. This study suggests that metabolic reprogramming in cancer cells enhances the potential of migration, invasion and proliferation. It also strengthens the cancer cells to escape the death processes, conferring resistance to therapeutic modalities. Our data also suggest that combining metabolic inhibitors like 2-DG with conventional therapeutic modalities can sensitize such metabolically aggressive cancer cells more than the therapies alone.

Keywords: 2-DG, BMG, DNP, OPM-BMG

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Authors: Agnieszka S. Dzielendziak, Lindsay-Marie Armstrong, Matthew E. Potter, Robert Raja, Pier J. A. Sazio

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Reducing carbon dioxide, CO₂, is one of the greatest global challenges. Conversion of CO₂ for utilisation across synthetic fuel, pharmaceutical, and agrochemical industries offers a promising option, yet requires significant research to understanding the complex multiscale processes involved. To experimentally understand and optimize such processes at that catalytic sites and exploring the impact of the process at reactor scale, is too expensive. Computational methods offer significant insight and flexibility but require a more detailed multi-scale approach which is a significant challenge in itself. This work introduces a computational approach which incorporates detailed catalytic models, taken from experimental investigations, into a larger-scale computational flow dynamics framework. The reactor-scale species transport approach is modified near the catalytic walls to determine the influence of catalytic clustering regions. This coupling approach enables more accurate modelling of velocity, pressures, temperatures, species concentrations and near-wall surface characteristics which will ultimately enable the impact of overall reactor design on chemical conversion performance.

Keywords: catalysis, CCU, CO₂, multi-scale model

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Authors: Abderrahmane Khiat, Moussa Benaissa

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Due to the increasing number of sources of information available on the web and their distribution and heterogeneity, ontology alignment became a very important and inevitable problem to ensure semantic interoperability. Instance-based ontology alignment is based on the comparison of the extensions of concepts; and represents a very promising technique to find semantic correspondences between entities of different ontologies. In practice, two situations may arise: ontologies that share many common instances and ontologies that share few or do not share common instances. In this paper, we describe an approach to manage the latter case. This approach exploits the reasoning on ontologies in order to create a corpus of common instances. We show that it is theoretically powerful because it is based on description logics and very useful in practice. We present the experimental results obtained by running our approach on ontologies of OAEI 2012 benchmark test. The results show the performance of our approach.

Keywords: description logic inference, instance-based ontology alignment, semantic interoperability, semantic web

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Authors: Fayaz Ali Shah, Aleena Shehzad

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The incidents of race or racial discrimination is still a part of the advanced and the so-called twenty-first-century America. It not only affects America's society but also greatly influences the third world countries due to the colonial approach by the British and America. Due to this discrimination, hundreds of Blacks in the US have been disappeared or prisoned for crimes they have not committed. The same sort of inequality can be seen in Pakistan due to the discrimination and prejudice by the Pakistani government and militants. Especially the tribal areas of Pakistan have been facing the worst in such situations. Thousands of people have been disappeared since 9/11 due to the adulterous approach by the government and military. The article is an approach to show the still racist view or Black marginalization, on the paradigm of racism, in the novel 'The Guardian' written by John Grisham. Also, it will enlighten readers about Pakistan's military and government approach towards discrimination, which creates great chaos in the country nowadays. The research will be qualitative and will use Critical Race Theory by Delgado and Steffencic for analysis.

Keywords: blacks, colonial, discrimination, disappeared, prison

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Authors: Mehrosadat Mirmohammadi, Sara Taghdisi, Ali Padash, Mohammad Hossein Pazandeh

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Gossypol, a yellowish anti-nutritional compound found in cotton plants, exists in various plant parts, including seeds, husks, leaves, and stems. Chemically, gossypol is a potent polyphenolic aldehyde with antioxidant and therapeutic properties. However, its free form can be toxic, posing risks to both humans and animals. Initially, we extracted gossypol from cotton seeds using n-hexane as a solvent (yield: 84.0 ± 4.0%). We also obtained cotton seed and cotton boll extracts via Soxhlet extraction (25:75 hydroalcoholic ratio). These extracts, combined with cornstarch, formed four herbal medicinal formulations. Ethical approval allowed us to investigate their effects on Leishmania-caused skin wounds, comparing them to glucantime (local ampoule). Herbal formulas outperformed the control group (ethanol only) in wound treatment (p-value 0.05). The average wound diameter after two months did not significantly differ between plant extract ointments and topical glucantime. Notably, cotton boll extract with 1% extra gossypol crystal showed the best therapeutic effect. We extracted gossypol from cotton seeds using n-hexane via Soxhlet extraction. Saponification, acidification, and recrystallization steps followed. FTIR, UV-Vis, and HPLC analyses confirmed the product’s identity. Herbal medicines from cotton seeds effectively treated chronic wounds compared to the ethanol-only control group. Wound diameter differed significantly between extract ointments and glucantime injections. It seems that due to the presence of large amounts of fat in the oil, the extraction of gossypol from it faces many obstacles. The extraction of this compound with our technique showed that extraction from oil has a higher efficiency, perhaps because of the preparation of oil by cold pressing method, the possibility of losing this compound is much less than when extraction is done with Soxhlet. On the other hand, the gossypol in the oil is mostly bound to the protein, which somehow protects the gossypol until the last stage of the extraction process. Since this compound is very sensitive to light and heat, it was extracted as a derivative with acetic acid. Also, in the treatment section, it was found that the ointment prepared with the extract is more effective and Gossypol is one of the effective ingredients in the treatment. Therefore, gossypol can be extracted from the oil and added to the extract from which gossypol has been extracted to make an effective medicine with a certain dose.

Keywords: cottonseed, glucantime, gossypol, leishmaniasis

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Authors: Temesgen Sidamo, Prakruti S. Rao, Eleni Akllilu, Workineh Shibeshi, Yumi Park, Yong-Soon Cho, Jae-Gook Shin, Scott K. Heysell, Stellah G. Mpagama, Ephrem Engidawork

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The fluoroquinolones (FQs) are used off-label for the treatment of multidrug-resistant tuberculosis (MDR-TB), and for evaluation in shortening the duration of drug-susceptible TB in recently prioritized regimens. Within the class, levofloxacin (LFX) and moxifloxacin (MXF) play a substantial role in ensuring success in treatment outcomes. However, sub-therapeutic plasma concentrations of either LFX or MXF may drive unfavorable treatment outcomes. To the best of our knowledge, the pharmacokinetics of LFX and MXF in Ethiopian patients with MDR-TB have not yet been investigated. Therefore, the aim of this study was to develop a population pharmacokinetic (PopPK) model of levofloxacin (LFX) and moxifloxacin (MXF) and assess the percent probability of target attainment (PTA) as defined by the ratio of the area under the plasma concentration-time curve over 24-h (AUC0-24) and the in vitro minimum inhibitory concentration (MIC) (AUC0-24/MIC) in Ethiopian MDR-TB patients. Steady-state plasma was collected from 39 MDR-TB patients enrolled in the programmatic treatment course and the drug concentrations were determined using optimized liquid chromatography-tandem mass spectrometry. In addition, the in vitro MIC of the patients' pretreatment clinical isolates was determined. PopPK and simulations were run at various doses, and PK parameters were estimated. The effect of covariates on the PK parameters and the PTA for maximum mycobacterial kill and resistance prevention was also investigated. LFX and MXF both fit in a one-compartment model with adjustments. The apparent volume of distribution (V) and clearance (CL) of LFX were influenced by serum creatinine (Scr), whereas the absorption constant (Ka) and V of MXF were influenced by Scr and BMI, respectively. The PTA for LFX maximal mycobacterial kill at the critical MIC of 0.5 mg/L was 29%, 62%, and 95% with the simulated 750 mg, 1000 mg, and 1500 mg doses, respectively, whereas the PTA for resistance prevention at 1500 mg was only 4.8%, with none of the lower doses achieving this target. At the critical MIC of 0.25 mg/L, there was no difference in the PTA (94.4%) for maximum bacterial kill among the simulated doses of MXF (600 mg, 800 mg, and 1000 mg), but the PTA for resistance prevention improved proportionately with dose. Standard LFX and MXF doses may not provide adequate drug exposure. LFX PopPK is more predictable for maximum mycobacterial kill, whereas MXF's resistance prevention target increases with dose. Scr and BMI are likely to be important covariates in dose optimization or therapeutic drug monitoring (TDM) studies in Ethiopian patients.

Keywords: population PK, PTA, moxifloxacin, levofloxacin, MDR-TB patients, ethiopia

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Authors: Isalira Peroba Ramos, Cherley Borba Vieira de Andrade, Grazielle Suhett, Camila Salata, Paulo Cesar Canary, Guilherme Visconde Brasil, Antonio Carlos Campos de Carvalho, Regina Coeli dos Santos Goldenberg

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Background: The therapeutic options for patients with cancer now include increasingly complex combinations of medications, radiation therapy (RT), and surgical intervention. Many of these treatments have important potential adverse cardiac effects and are likely to have significant effects on patient outcomes. Cell therapy appears to be promising for the treatment of chronic and degenerative diseases, including cardiomyopathy induced by RT, as the current therapeutic options are insufficient. Aims: To evaluate the potential of bone marrow mesenchymal cells (BMMCs) in radioinduced cardiac damage Methods: Female Wistar rats, 3 months old (Ethics Committee 054/14), were divided into 2 groups, non-treated irradiated group (IR n=15) and irradiated and BMMC treated (IRT n=10). Echocardiography was performed to evaluate heart function. After euthanasia, 3 months post treatment; the left ventricle was removed and prepared for RT-qPCR (VEGF and Pro Collagen I) and histological (picrosirius) analysis. Results: In both groups, 45 days after irradiation, ejection fraction (EF) was in the normal range for these animals (> 70%). However, the BMMC treated group had EF (83.1%±2.6) while the non-treated IR group showed a significant reduction (76.1%±2.6) in relation to the treated group. In addition, we observed an increase in VEGF gene expression and a decrease in Pro Collagen I in IRT when compared to IR group. We also observed by histology that the collagen deposition was reduced in IRT (10.26%±0.83) when compared to IR group (25.29%±0.96). Conclusions: Treatment with BMMCs was able to prevent ejection fraction reduction and collagen deposition in irradiated animals. The increase of VEGF and the decrease of pro collagen I gene expression might explain, at least in part, the cell therapy benefits. All authors disclose no financial or personal relationships with individuals or organizations that could be perceived to bias their work. Sources of funding: FAPERJ, CAPES, CNPq, MCT.

Keywords: mesenchymal cells, radioation, cardiotoxicity, bone marrow

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Authors: L. Belounar, K. Gerraiche, C. Rebiai, S. Benmebarek

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This paper presents the development of a new three dimensional brick finite element by the use of the strain based approach for the linear analysis of plate bending behavior. The developed element has the three essential external degrees of freedom (U, V and W) at each of the eight corner nodes. The displacements field of the developed element is based on assumed functions for the various strains satisfying the compatibility and the equilibrium equations. The performance of this element is evaluated on several problems related to thick and thin plate bending in linear analysis. The obtained results show the good performances and accuracy of the present element.

Keywords: brick element, strain approach, plate bending, civil engineering

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Authors: Bruno Baptista, Andreia S. R. Oliveira, Patricia V. Mendonca, Jorge F. J. Coelho, Fani Sousa

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Drug delivery systems are designed to allow adequate protection and controlled delivery of drugs to specific locations. These systems aim to reduce side effects and control the biodistribution profile of drugs, thus improving therapeutic efficacy. This study involved the synthesis of polymeric nanoparticles, based on amphiphilic diblock copolymers, comprising a biocompatible, poly (oligo (ethylene oxide) methyl ether methacrylate (POEOMA) as hydrophilic segment and a pH-sensitive block, the poly (2-diisopropylamino)ethyl methacrylate) (PDPA). The objective of this work was the development of polymeric pH-responsive nanoparticles to encapsulate and carry small RNAs as a model to further develop non-coding RNAs delivery systems with therapeutic value. The responsiveness of PDPA to pH allows the electrostatic interaction of these copolymers with nucleic acids at acidic pH, as a result of the protonation of the tertiary amine groups of this polymer at pH values below its pKa (around 6.2). Initially, the molecular weight parameters and chemical structure of the block copolymers were determined by size exclusion chromatography (SEC) and nuclear magnetic resonance (1H-NMR) spectroscopy, respectively. Then, the complexation with small RNAs was verified, generating polyplexes with sizes ranging from 300 to 600 nm and with encapsulation efficiencies around 80%, depending on the molecular weight of the polymers, their composition, and concentration used. The effect of pH on the morphology of nanoparticles was evaluated by scanning electron microscopy (SEM) being verified that at higher pH values, particles tend to lose their spherical shape. Since this work aims to develop systems for the delivery of non-coding RNAs, studies on RNA protection (contact with RNase, FBS, and Trypsin) and cell viability were also carried out. It was found that they induce some protection against constituents of the cellular environment and have no cellular toxicity. In summary, this research work contributes to the development of pH-sensitive polymers, capable of protecting and encapsulating RNA, in a relatively simple and efficient manner, to further be applied on drug delivery to specific sites where pH may have a critical role, as it can occur in several cancer environments.

Keywords: drug delivery systems, pH-responsive polymers, POEOMA-b-PDPA, small RNAs

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Authors: Manel Brichni, Abdelhak-Djamel Seriai

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Systems are increasingly complex. To reduce their complexity, an abstract view of the system can simplify its development. To overcome this problem, we propose a method to decompose systems into subsystems while reducing their coupling. These subsystems represent components. Consisting of an existing object-oriented systems, the main idea of our approach is based on modelling as graphs all entities of an oriented object source code. Such modelling is easy to handle, so we can apply restructuring algorithms based on graph metrics. The particularity of our approach consists in integrating in addition to standard metrics, such as coupling and cohesion, some graph metrics giving more precision during the components identication. To treat this problem, we relied on the ROMANTIC approach that proposed a component-based software architecture recovery from an object oriented system.

Keywords: software reengineering, software component and interfaces, metrics, graphs

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Authors: Lacramioara Ochiuz, Aurelia Vasile, Iulian Stoleriu, Cristina Ghiciuc, Maria Ignat

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Topical administration of chemotherapeutic agents (eg. carmustine, bexarotene, mechlorethamine etc.) in local treatment of cutaneous T-cell lymphoma (CTCL) is accompanied by multiple side effects, such as contact hypersensitivity, pruritus, skin atrophy or even secondary malignancies. A known method of reducing the side effects of anticancer agent is the development of modified drug release systems using drug incapsulation in biocompatible nanoporous inorganic matrices, such as mesoporous MCM-41 silica. Mesoporous MCM-41 silica is characterized by large specific surface, high pore volume, uniform porosity, and stable dispersion in aqueous medium, excellent biocompatibility, in vivo biodegradability and capacity to be functionalized with different organic groups. Therefore, MCM-41 is an attractive candidate for a wide range of biomedical applications, such as controlled drug release, bone regeneration, protein immobilization, enzymes, etc. The main advantage of this material lies in its ability to host a large amount of the active substance in uniform pore system with adjustable size in a mesoscopic range. Silanol groups allow surface controlled functionalization leading to control of drug loading and release. This study shows (I) the amino-grafting optimization of mesoporous MCM-41 silica matrix by means of co-condensation during synthesis and post-synthesis using APTES (3-aminopropyltriethoxysilane); (ii) loading the therapeutic agent (carmustine) obtaining a modified drug release systems; (iii) determining the profile of in vitro carmustine release from these systems; (iv) assessment of carmustine release kinetics by fitting on four mathematical models. Obtained powders have been described in terms of structure, texture, morphology thermogravimetric analysis. The concentration of the therapeutic agent in the dissolution medium has been determined by HPLC method. In vitro dissolution tests have been done using cell Enhancer in a 12 hours interval. Analysis of carmustine release kinetics from mesoporous systems was made by fitting to zero-order model, first-order model Higuchi model and Korsmeyer-Peppas model, respectively. Results showed that both types of highly ordered mesoporous silica (amino grafted by co-condensation process or post-synthesis) are thermally stable in aqueous medium. In what regards the degree of loading and efficiency of loading with the therapeutic agent, there has been noticed an increase of around 10% in case of co-condensation method application. This result shows that direct co-condensation leads to even distribution of amino groups on the pore walls while in case of post-synthesis grafting many amino groups are concentrated near the pore opening and/or on external surface. In vitro dissolution tests showed an extended carmustine release (more than 86% m/m) both from systems based on silica functionalized directly by co-condensation and after synthesis. Assessment of carmustine release kinetics revealed a release through diffusion from all studied systems as a result of fitting to Higuchi model. The results of this study proved that amino-functionalized mesoporous silica may be used as a matrix for optimizing the anti-cancer topical therapy by loading carmustine and developing prolonged-release systems.

Keywords: carmustine, silica, controlled, release

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Authors: Sudeshna Mukherjee, Leena Fageria, R. Venkataramana Dilip, Rajdeep Chowdhury, Jitendra Panwar

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Metal nanoparticles in recent years have gained importance in cancer therapy due to their enhanced permeability retention effect. Among various nanomaterials, silver nanoparticles (AgNPs) have received considerable attention due to their unique properties like conductivity, chemical stability, relative lower toxicity and outstanding therapeutic potential, such as anti-inflammatory, antimicrobial and anti-cancerous activities. In this study, we took a greener approach to synthesize silver nanoparticle from fungus and analyze its effects on both epithelial and mesenchymal derived cancer cells. Much research has been done on nanoparticle-induced apoptosis, but little is known about its role in autophagy. In our study, the silver nanoparticles were seen to induce autophagy which was analyzed by studying the expression of several autophagy markers like, LC3B-II and ATG genes. Monodansylcadaverine (MDC) assay also revealed the induction of autophagy upon treatment with AgNPs. Inhibition of autophagy by chloroquine resulted in increased cell death suggesting autophagy as a survival strategy adopted by the cells. In parallel to autophagy induction, silver nanoparticles induced ROS accumulation. Interestingly, autophagy inhibition by chloroquine increased ROS level, resulting in enhanced cell death. We further analyzed MAPK signaling upon AgNP treatment. It was observed that along with autophagy, activation of JNK signaling served as pro-survival while ERK signaling served as a pro-death signal. Our results provide valuable insights into the role of autophagy upon AgNP exposure and provide cues to probabilistic strategies to effectively sensitize cancer cells.

Keywords: autophagy, JNK signalling, reactive oxygen species, silver nanoparticles

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Authors: Maali Kachouri, Anis Jarboui

Abstract:

We focus on the causal relationship between governance and information transparency as well as interrelation among the various governance mechanisms. This paper employs a simultaneous equations approach to show this relationship in the Tunisian context. Based on an 8-year dataset, our sample covers 28 listed companies over 2006-2013. Our findings suggest that internal and external governance mechanisms are interdependent. Moreover, in order to analyze the causal effect between information transparency and governance mechanisms, we found evidence that information transparency tends to increase good corporate governance practices.

Keywords: simultaneous equations approach, transparency, causal relationship, corporate governance

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Authors: Nakache Radouane, M. Boukelloul, M. Fredj

Abstract:

Method room and pillar sizes are key factors for safe mining and their recovery in open-stop mining. This method is advantageous due to its simplicity and requirement of little information to be used. It is probably the most representative method among the total load approach methods although it also remains a safe design method. Using a finite element software (PLAXIS 3D), analyses were carried out with an elasto-plastic model and comparisons were made with methods based on the total load approach. The results were presented as the optimization for improving the ore recovery rate while maintaining a safe working environment.

Keywords: room and pillar, mining, total load approach, elasto-plastic

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Authors: Daniel C. Bonzo

Abstract:

Practical considerations lead to the use of unit of analysis within subjects, e.g., bleeding episodes or treatment-related adverse events, in rare disease settings. This is coupled with data augmentation techniques such as extrapolation to enlarge the subject base. In general, one can think about extrapolation of data as extending information and conclusions from one estimand to another estimand. This approach induces hierarchichal clustered data with varying cluster sizes. Extrapolation of clinical trial data is being accepted increasingly by regulatory agencies as a means of generating data in diverse situations during drug development process. Under certain circumstances, data can be extrapolated to a different population, a different but related indication, and different but similar product. We consider here the problem of estimation (point and interval) using a mixed-models approach under an extrapolation. It is proposed that estimators (point and interval) be constructed using weighting schemes for the clusters, e.g., equally weighted and with weights proportional to cluster size. Simulated data generated under varying scenarios are then used to evaluate the performance of this approach. In conclusion, the evaluation result showed that the approach is a useful means for improving statistical inference in rare disease settings and thus aids not only signal detection but risk-benefit evaluation as well.

Keywords: clustered data, estimand, extrapolation, mixed model

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Authors: Chander Kant, Arun Kumar

Abstract:

Biometric systems automatically recognize an individual based on his/her physiological and behavioral characteristics. There are also some traits like weight, age, height etc. that may not provide reliable user recognition because of there common and temporary nature. These traits are called soft bio metric traits. Although soft bio metric traits are lack of permanence to uniquely and reliably identify an individual, yet they provide some beneficial evidence about the user identity and may improve the system performance. Here in this paper, we have proposed an approach for integrating the soft bio metrics with fingerprint and face to improve the performance of personal authentication system. In our approach we have proposed a combined architecture of three different sensors to elevate the system performance. The approach includes, soft bio metrics, fingerprint and face traits. We have also proven the efficiency of proposed system regarding FAR (False Acceptance Ratio) and total response time, with the help of MUBI (Multimodal Bio metrics Integration) software.

Keywords: FAR, minutiae point, multimodal bio metrics, primary bio metric, soft bio metric

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Authors: Hsin-Yi Huang, Ming-Sheng Liu, Jiun-Yan Shiau

Abstract:

Planning the order picking lists of warehouses to achieve when the costs associated with logistics on the operational performance is a significant challenge. In e-commerce era, this task is especially important productive processes are high. Nowadays, many order planning techniques employ supervised machine learning algorithms. However, the definition of which features should be processed by such algorithms is not a simple task, being crucial to the proposed technique’s success. Against this background, we consider whether unsupervised algorithms can enhance the planning of order-picking lists. A Zone2 picking approach, which is based on using clustering algorithms twice, is developed. A simplified example is given to demonstrate the merit of our approach.

Keywords: order picking, warehouse, clustering, unsupervised learning

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Authors: Haris Karnezi, Kevin Tierney

Abstract:

Cognitive Behaviour Drama is a research-based intervention model that brought together the science of psychology with the art form of drama to create an unobtrusive and exciting approach that would provide children on the higher end of the autism spectrum the motivation to explore the rules of social interaction and develop competencies associated with communicative success. The method involves engaging the participants in exciting fictional scenarios and encouraging them to seek various solutions on a number of problems that will lead them to an understanding of causal relationships and how a different course of action may lead to a different outcome. The sessions are structured to offer opportunities to the participants to practice target behaviours and understand the functions they serve. The study involved six separate interventions and employed both single case and group designs. Overall 8 children aged between 6 to 13 years, diagnosed with ASD participated in the study. Outcomes were measured using theory of mind tests, executive functioning tests, behavioural observations, pre and post intervention standardised social competence questionnaires for parents and teachers. Collectively, the results indicated positive changes in the self esteem and behaviour of all eight participants. In particular, improvements in the ability to solve theory of mind tasks were noted in the younger group; and qualitative improvements in social communication, in terms of verbal (content) and non verbal expression (body posture, vocal expression, fluency, eye contact, reduction of ritualistic mannerisms) were noted in the older group. The need for reliable impact measures to assess the effectiveness of the model in generating global changes in the participants’ behaviour outside the therapeutic context was identified.

Keywords: autism, drama, intervention, social skills

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Authors: D. Motlhanka, M. Mine, T. Bagaketse, T. Ngakane

Abstract:

There is a plethora of evidence from numerous sources that highlights the triumph of naturally derived medicinal plant metabolites with antioxidant capability for repurposed therapeutics. As post-COVID-19 syndromes and non-communicable diseases are on the rise, there is an urgent need to come up with new therapeutic strategies to address the problem. Non-communicable diseases and Post COVID-19 syndromes are classified as socio-economic diseases and are ranked high among threats to health security due to the economic burden they pose to any government budget commitment. Research has shown a strong link between accumulation of free radicals and oxidative stress critical for pathogenesis of non-communicable diseases and COVID-19 syndromes. Botswana has embarked on a robust programme derived from ethno-pharmacognosy and drug repurposing to address these threats to health security. In the current approach, a number of medicinally active plant-derived polyphenolics are repurposed and combined into new medicinal tools to target diabetes, Hypertension, Prostate Cancer and oxidative stress induced Post COVID 19 syndromes such as “brain fog”. All four formulants demonstrated Free Radical scavenging capacities above 95% at 200µg/ml using the diphenylpicryalhydrazyl free radical scavenging assay and the total phenolic contents between 6899-15000GAE(g/L) using the folin-ciocalteau assay respectively. These repurposed medicinal tools offer new hope and potential in the fight against emerging health threats driven by hyper-inflammation and free radical-induced oxidative stress.

Keywords: drug repurposed plant polyphenolics, free radical damage, non-communicable diseases, post COVID 19 syndromes

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