Search results for: Uputaua therapeutic approach
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 14547

Search results for: Uputaua therapeutic approach

14187 Pharmaceutical Equivalence of Some Injectable Gentamicin Generics Used in Veterinary Practice in Nigeria

Authors: F. A. Gberindyer, M. O.Abatan, A. B. Saba

Abstract:

Background: Gentamicin is an aminoglycoside antibiotic used in the treatment of infections caused by Gram-negative aerobic bacteria organisms in human and animals. In Nigeria, there are arrays of multisource generic versions of injectable gentamicin sulphate in the drug markets. There is a high prevalence of counterfeit and substandard drugs in the third world countries with consequent effect on their therapeutic efficacy and safety. Aim: The aim of this study was to investigate pharmaceutical equivalence of some of these generics used in veterinary practice in Nigeria. Methodology: About 20 generics of injectable gentamicin sulphate were sampled randomly across Nigeria but 15 were analyzed for identity and potency. Identity test was done using Fourier transform infra red spectroscopy and the spectral for each product compared with that of the USP reference standard for similarity. Microbiological assay using agar diffusion method with E. coli as a test organism on nutrient agar was employed and the respective diameters of bacterial inhibition zones obtained after 24 hour incubation at 37°C. The percent potency for each product was thereafter calculated and compared with the official specification. Result And Discussion: None of the generics is produced in any African country. About 75 % of the products are imported from China whereas 60 % of the veterinary generics are manufactured in Holland. Absorption spectra for the reference and test samples were similar. Percent potencies of all test products were within the official specification of 95-115 %. Nigeria relies solely on imported injectable gentamicin sulphate products. All sampled generic versions passed both identity and potency tests. Clinicians should ensure that drugs are used rationally since the converse could be contributing to the therapeutic failures reported for most of these generics. Bioequivalence study is recommended to ascertain their interchangeability when parenteral extra venous routes are indicated.

Keywords: generics, gentamicin, identity, multisource, potency

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14186 Examination of the Impact of Projects Based on Reggio Emilia Approach on the Creative Thinking Skills of Preschool Children: A Qualitative Study

Authors: Arzu Akar Gençer, Mübeccel Gönen

Abstract:

The objective of the study is to investigate the impact of the projects based on Reggio Emilia Approach, on the creative thinking skills of preschool children. The study is carried out with eighteen 6 years old children in a class of a preschool, and entailed the development of projects based on Reggio Emilia approach with the children, for a period of 3 months. The study employs qualitative model. The children were analyzed with reference to the creative thinking aspects (rationality, originality, flexibility, and applicability) of the projects applied. As the projects based on Reggio Emilia approach arose out of the interests and curiosity of the children, and had their roots in the existing class culture, it is possible to conclude that they have an impact on the creativity of the children with reference to the aspects of creative thinking.

Keywords: Reggio Emilia approach, project, creativity, preschool children

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14185 Education of Mothers and Influence on the Development of Intrauterine Growth Restriction

Authors: Sabina Garayeva

Abstract:

To determine the significant risk factors for intrauterine growth restriction (IUGR), we carried out a thorough study of the social status of the parents of children with IUGR. We observed 315 mothers who gave birth to children with (IUGR), of which 172 mothers with asymmetric type and 143 mothers with symmetric type of IUGR. Through a detailed survey was gathered detailed information about education of parents. The results show that the majority of mothers with IUGR had secondary education (44,8 ± 2,8%), and fathers - higher education (35,2 ± 2,7%). Whereas in the control group, the largest number of parents had higher education (mother 35,3 ± 4,4%, fathers 42,9 ± 4,5%). Number of mothers with secondary education with IUGR was significantly (p1 <0,01; χ2 = 22,67) differs from the number of mothers with physiological pregnancy with the same level of education. Meanwhile, in the group with a symmetrical embodiment of IUGR mothers with secondary formation of significantly greater 53,1 ± 4,2%, than the asymmetric embodiment IUGR 37,8 ± 3,7% (p2 <0,05; χ2 = 8 06). Among fathers with secondary education significant difference was noted in the symmetric version of IUGR 37,8 ± 4,1% more than in the control group (p1 <0,05), and among parents of children with asymmetric IUGR option prevailed fathers with higher education - 37 2 ± 3,7%. Thus, our results revealed a low educational level of the mother as a risk factor for IUGR, which further help to develop preventive and therapeutic measures to eliminate the severity of its consequences. As seen from the data presented, mothers of children with asymmetric IUGR had a school education and fathers - higher education, while in the symmetric type of both parents had secondary education. It is found that frequency of children, born with IUGR, of mothers - housewives and fathers, engage in physical labor, was high. Thus, the analysis conducted by the social status of the parents with IUGR revealed a low level of education and unemployed mothers as risk factors for this disease, which in the future will help to develop preventive and therapeutic measures to eliminate the severity of its.

Keywords: intrauterine growth restriction, education of mothers, education influence, IUGR

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14184 Multifunctional Janus Microbots for Intracellular Delivery of Therapeutic Agents

Authors: Shilpee Jain, Sachin Latiyan, Kaushik Suneet

Abstract:

Unlike traditional robots, medical microbots are not only smaller in size, but they also possess various unique properties, for example, biocompatibility, stability in the biological fluids, navigation opposite to the bloodstream, wireless control over locomotion, etc. The idea behind their usage in the medical field was to build a minimally invasive method for addressing the post-operative complications, including longer recovery time, infection eruption and pain. Herein, the present study demonstrates the fabrication of dual nature magneto-conducting Fe3O4 magnetic nanoparticles (MNPs) and SU8 derived carbon-based Janus microbots for the efficient intracellular delivery of biomolecules. The low aspect ratio with feature size 2-5 μm microbots were fabricated by using a photolithography technique. These microbots were pyrolyzed at 900°C, which converts SU8 into amorphous carbon. The pyrolyzed microbots have dual properties, i.e., the half part is magneto-conducting and another half is only conducting for sufficing the therapeutic payloads efficiently with the application of external electric/magnetic field stimulations. For the efficient intracellular delivery of the microbots, the size and aspect ratio plays a significant role. However, on a smaller scale, the proper control over movement is difficult to achieve. The dual nature of Janus microbots allowed to control its maneuverability in the complex fluids using external electric as well as the magnetic field. Interestingly, Janus microbots move faster with the application of an external electric field (44 µm/s) as compared to the magnetic field (18 µm/s) application. Furthermore, these Janus microbots exhibit auto-fluorescence behavior that will help to track their pathway during navigation. Typically, the use of MNPs in the microdevices enhances the tendency to agglomerate. However, the incorporation of Fe₃O₄ MNPs in the pyrolyzed carbon reduces the chances of agglomeration of the microbots. The biocompatibility of the medical microbots, which is the essential property of any biosystems, was determined in vitro using HeLa cells. The microbots were found to compatible with HeLa cells. Additionally, the intracellular uptake of microbots was higher in the presence of an external electric field as compared to without electric field stimulation. In summary, the cytocompatible Janus microbots were fabricated successfully. They are stable in the biological fluids, wireless controllable navigation with the help of a few Guess external magnetic fields, their movement can be tracked because of autofluorescence behavior, they are less susceptible to agglomeration and higher cellular uptake could be achieved with the application of the external electric field. Thus, these carriers could offer a versatile platform to suffice the therapeutic payloads under wireless actuation.

Keywords: amorphous carbon, electric/magnetic stimulations, Janus microbots, magnetic nanoparticles, minimally invasive procedures

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14183 A Bundled Approach to Explaining Technological Change: The Case of E-Estonia

Authors: Andrew Adjah Sai, Portia Opoku Boadi

Abstract:

Explaining change is an abstract endeavor. Many management scholars have adopted metaphors to explain change. In this paper, we deal with the drivers of technological change. We use a historical and theoretical approach to review and elaborate on the concepts and context about a specific case. We discuss the limitations of each approach proffered and the implications as a consequence on technological change. We present plurality and multiplicity of perspectives using a socio-technical approach to explain technological change contextually on an organizational level. We show by using our model how technology absorption and diffusion can be accelerated through artefactual institutions to enable social change. The multiplicity of perspectives and plurality of our arguments creates a fine explanation of the e-Estonia case as an example.

Keywords: artefactual institutions, e-Estonia, social change, technological trajectories

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14182 Mannose-Functionalized Lipopolysaccharide Nanoparticles for Macrophage-Targeted Dual Delivery of Rifampicin and Isoniazid

Authors: Mumuni Sumaila, Viness Pillay, Yahya E. Choonara, Pradeep Kumar, Pierre P. Kondiah

Abstract:

Tuberculosis (TB) remains a serious challenge to public health globally, despite every effort put together to curb the disease. Current TB therapeutics available have proven to be inefficient due to a multitude of drawbacks that range from serious adverse effects/drug toxicity to inconsistent bioavailability, which ultimately contributes to the emergence of drug-resistant TB. An effective ‘cargo’ system designed to cleverly deliver therapeutic doses of anti-TB drugs to infection sites and in a sustained-release manner may provide a better therapeutic choice towards winning the war against TB. In the current study, we investigated mannose-functionalized lipopolysaccharide hybrid nanoparticles for safety and efficacy towards macrophage-targeted simultaneous delivery of the two first-line anti-TB drugs, rifampicin (RF) and isoniazid (IS). RF-IS-loaded lipopolysaccharide hybrid nanoparticles were fabricated using the solvent injection technique (SIT), incorporating soy lecithin (SL) and low molecular weight chitosan (CS) as the lipid and polysaccharide components, respectively. Surface-functionalized nanoparticles were obtained through the reaction of the aldehyde group of mannose with free amine functionality present at the surface of the nanoparticles. The functionalized nanocarriers were spherical with average particle size and surface charge of 107.83 nm and +21.77 mV, respectively, and entrapment efficiencies (EE) were 53.52% and 69.80% for RF and IS, respectively. FTIR spectrum revealed high-intensity bands between 1663 cm⁻¹ and 1408 cm⁻¹ wavenumbers (absent in non-functionalized nanoparticles), which could be attributed to the C=N stretching vibration produced by the formation of Schiff’s base (–N=CH–) during the mannosylation reaction. In vitro release studies showed a sustained-release profile for RF and IS, with less than half of the total payload released over a 48-hour period. The nanocarriers were biocompatible and safe, with more than 80% cell viability achieved when incubated with RAW 264.7 cells at concentrations 30 to 500 μg/mL over a 24-hour period. Cellular uptake studies (after a 24-hour incubation period with the murine macrophage cells, RAW 264.7) revealed a 13- and a 9-fold increase in intracellular accumulation of RF and IS, respectively, when compared with the unformulated RF+IS solution. A 6- and a 3-fold increase in intracellular accumulation of RF and IS, respectively, were observed when compared with the non-functionalized nanoparticles. Furthermore, fluorescent microscopy images showed nanoparticle internalization and accumulation within the RAW 264.7 cells, which was more significant in the mannose-functionalized system compared to the non-functionalized nanoparticles. The overall results suggested that the fabricated mannose-functionalized lipopolysaccharide nanoparticles are a safe and promising platform for macrophage-targeted delivery of anti-TB therapeutics. However, in vivo pharmacokinetic/pharmacodynamics studies are required to further substantiate the therapeutic efficacy of the nanosystem.

Keywords: anti-tuberculosis therapeutics, hybrid nanosystem, lipopolysaccharide nanoparticles, macrophage-targeted delivery

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14181 Effectiveness, Safety, and Tolerability Profile of Stribild® in HIV-1-infected Patients in the Clinical Setting

Authors: Heiko Jessen, Laura Tanus, Slobodan Ruzicic

Abstract:

Objectives: The efficacy of Stribild®, an integrase strand transfer inhibitor (INSTI) -based STR, has been evaluated in randomized clinical trials and it has demonstrated durable capability in terms of achieving sustained suppression of HIV-1 RNA-levels. However, differences in monitoring frequency, existing selection bias and profile of patients enrolled in the trials, may all result in divergent efficacy of this regimen in routine clinical settings. The aim of this study was to assess the virologic outcomes, safety and tolerability profile of Stribild® in a routine clinical setting. Methods: This was a retrospective monocentric analysis on HIV-1-infected patients, who started with or were switched to Stribild®. Virological failure (VF) was defined as confirmed HIV-RNA>50 copies/ml. The minimum time of follow-up was 24 weeks. The percentage of patients remaining free of therapeutic failure was estimated using the time-to-loss-of-virologic-response (TLOVR) algorithm, by intent-to-treat analysis. Results: We analyzed the data of 197 patients (56 ART-naïve and 141 treatment-experienced patients), who fulfilled the inclusion criteria. Majority (95.9%) of patients were male. The median time of HIV-infection at baseline was 2 months in treatment-naïve and 70 months in treatment-experienced patients. Median time [IQR] under ART in treatment-experienced patients was 37 months. Among the treatment-experienced patients 27.0% had already been treated with a regimen consisting of two NRTIs and one INSTI, whereas 18.4% of them experienced a VF. The median time [IQR] of virological suppression prior to therapy with Stribild® in the treatment-experienced patients was 10 months [0-27]. At the end of follow-up (median 33 months), 87.3% (95% CI, 83.5-91.2) of treatment-naïve and 80.3% (95% CI, 75.8-84.8) of treatment-experienced patients remained free of therapeutic failure. Considering only treatment-experienced patients with baseline VL<50 copies/ml, 83.0% (95% CI, 78.5-87.5) remained free of therapeutic failure. A total of 17 patients stopped treatment with Stribild®, 5.4% (3/56) of them were treatment-naïve and 9.9% (14/141) were treatment-experienced patients. The Stribild® therapy was discontinued in 2 (1.0%) because of VF, loss to follow-up in 4 (2.0%), and drug-drug interactions in 2 (1.0%) patients. Adverse events were in 7 (3.6%) patients the reason to switch from therapy with Stribild® and further 2 (1.0%) patients decided personally to switch. The most frequently observed adverse events were gastrointestinal side effects (20.0%), headache (8%), rash events (7%) and dizziness (6%). In two patients we observed an emergence of novel resistances in integrase-gene. The N155H evolved in one patient and resulted in VF. In another patient S119R evolved either during or shortly upon switch from therapy with Stribild®. In one further patient with VF two novel mutations in the RT-gene were observed when compared to historical genotypic test result (V106I/M and M184V), whereby it is not clear whether they evolved during or already before the switch to Stribild®. Conclusions: Effectiveness of Stribild® for treatment-naïve patients was consistent with data obtained in clinical trials. The safety and tolerability profile as well as resistance development confirmed clinical efficacy of Stribild® in a daily practice setting.

Keywords: ART, HIV, integrase inhibitor, stribild

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14180 Non-Destructive Visual-Statistical Approach to Detect Leaks in Water Mains

Authors: Alaa Al Hawari, Mohammad Khader, Tarek Zayed, Osama Moselhi

Abstract:

In this paper, an effective non-destructive, non-invasive approach for leak detection was proposed. The process relies on analyzing thermal images collected by an IR viewer device that captures thermo-grams. In this study a statistical analysis of the collected thermal images of the ground surface along the expected leak location followed by a visual inspection of the thermo-grams was performed in order to locate the leak. In order to verify the applicability of the proposed approach the predicted leak location from the developed approach was compared with the real leak location. The results showed that the expected leak location was successfully identified with an accuracy of more than 95%.

Keywords: thermography, leakage, water pipelines, thermograms

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14179 Reduction of Transient Receptor Potential Vanilloid 1 for Chronic Pain and Depression Co-Morbidity through Electroacupuncture and Gene Deletion in Mice Brain

Authors: Bernice Lottering, Yi-Wen Lin

Abstract:

Chronic pain and depression have an estimated 80% rate of comorbidity with unsatisfactory treatment interventions signifying the importance of developing effective therapeutic interventions for a serious chronic condition affecting a large majority of the global population. Chronic pain is defined as persistent pain presenting for over 3 months. This disease state increases the risk of developing depression in comparison to healthy individuals. In the current study, complete Freund’s adjuvant (CFA) was used to induce cell-mediated chronic inflammatory pain in a murine model. Significant mechanical and thermal hyperalgesia was induced, alongside observable depression-like behaviors. These conditions were attenuated through the use of electroacupuncture (EA). Similarly, these effects were also investigated with respect to the transient receptor potential vanilloid 1 (TRPV1), by analyzing the effects of TRPV1 gene deletion on the comorbidity of chronic pain and depression. The expression of the TRPV1 inflammatory response, and related downstream molecules, including protein kinases (PKs), mitogen-activated protein kinase (MAPKs), and transcriptional factors, were significantly reduced in the thalamus, prefrontal cortex (PFC), hippocampus, and periaqueductal gray (PAG) of CFA-treated mice. In addition, phosphorylated N-methyl-D-aspartate (NMDA) receptor 1 was also found to be reduced in the aforementioned areas, suggesting potential application and validity in a clinical setting. Our study determined the prospective therapeutic effects of EA in the treatment of chronic inflammatory pain and depression comorbidity and provides a novel and detailed mechanism underlying EA-mediated analgesia. These findings may be relevant in the utilization of clinical intervention approaches related to chronic pain and depression comorbidity.

Keywords: chronic pain, depression, NMDA, prefrontal cortex, TRPV1

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14178 Optimization of Switched Reluctance Motor for Drive System in Automotive Applications

Authors: A. Peniak, J. Makarovič, P. Rafajdus, P. Dúbravka

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The purpose of this work is to optimize a Switched Reluctance Motor (SRM) for an automotive application, specifically for a fully electric car. A new optimization approach is proposed. This unique approach transforms automotive customer requirements into an optimization problem, based on sound knowledge of a SRM theory. The approach combines an analytical and a finite element analysis of the motor to quantify static nonlinear and dynamic performance parameters, as phase currents and motor torque maps, an output power and power losses in order to find the optimal motor as close to the reality as possible, within reasonable time. The new approach yields the optimal motor which is competitive with other types of already proposed motors for automotive applications. This distinctive approach can also be used to optimize other types of electrical motors, when parts specifically related to the SRM are adjusted accordingly.

Keywords: automotive, drive system, electric car, finite element method, hybrid car, optimization, switched reluctance motor

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14177 Strengthening Deradicalizing Islamist Extremism in Indonesia: A Victim-Centred Approach

Authors: Milda Istiqomah

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Deradicalization program has long been the subject of investigation. There is a steadily growing interest in examining the results on how Islamist terrorists agree to abandon violence and leave radicalism; however, it is argued that de-radicalization program on terrorism in many countries is still questionable for its effectiveness. This article aims to provide an overview of the deradicalization program specifically related to the victim-centred approach conducted by the Indonesian government and investigates critical issues surrounding the analysis of their effectiveness and outcomes. This research employs several case studies of a victim-centred approach conducted by the Indonesian Witness and Victim Protection Agency as well as the Indonesian Counter-terrorism Agency. This paper argues that the victim-centred approach to de-radicalize former terrorist prisoners faces several implemental challenges; however, the initiative may offer promise for future successful de-radicalization program. Furthermore, until more data surrounding the efficacy of this initiative available, the victim-centred approach may also constitute a significant and essential component of disengagement, de-radicalisation, and reintegration of terrorist prisoners. In conclusion, this paper suggests that further empirical research concerning prevention policies and disengagement interventions related to victim-centred approach need to be explored to give more inputs to the Indonesian government to achieve the effectiveness of de-radicalization program.

Keywords: terrorism, victim-centred approach, de-radicalization, Islamist extremism

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14176 Endometrioma Ethanol Sclerotherapy

Authors: Lamia Bensissaid

Abstract:

Goals: Endometriosis affects 6 to 10% of women of childbearing age. 17 to 44% of them have ovarian endometriomas. Medical and surgical treatments represent the two therapeutic axes with which PMA can be associated. Laparoscopic intraperitoneal ovarian cystectomy is described as the reference technique in the management of endometriomas by learned societies (CNGOF, ESHRE, NICE). However, it leads to a significant short-term reduction in the AMH level and the number of antral follicles, especially in cases of bilateral cystectomy, large cyst size or cystectomy after recurrence. Often, the disease is at an advanced stage with several surgical patients. Most have adhesions, which increase the risk of surgical complications and suboptimal resection and, therefore recurrence of the cyst. These results led to a change of opinion towards a conservative approach. Sclerotherapy is an old technique which acts by fibrinoid necrosis. It consists of injecting a sclerosing agent into the cyst cavity. Results : Recurrence was less than 15% for a 12-month follow-up; these rates are comparable to those of surgery. It does not seem to have a negative impact on ovarian reserve, but this is not sufficiently evaluated. It has an advantage in IVF pregnancy rates compared to cystectomy, particularly in cases of recurrent endometriomas. It has the advantages: · To be done on an outpatient basis. · To be inexpensive. · To avoid sometimes difficult and iterative surgery: · To allow an increase in pregnancy rates and the preservation of the ovarian reserve compared to iterative surgery. · of great interest in cases of bilateral endometriomas (kissing ovaries) or recurrent endometriomas. Conclusions: Ethanol sclerotherapy could be a good alternative to surgery.

Keywords: Endometrioma, Sclerotherapy, infertility, Ethanol

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14175 The “Ecological Approach” to GIS Implementation in Low Income Countries’ and the Role of Universities: Union of Municipalities of Joumeh Case Study

Authors: A. Iaaly, O. Jadayel, R. Jadayel

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This paper explores the effectiveness of approaches used for the implementation of technology within central governments specifically Geographic Information Systems (GIS). It examines the extent to which various strategies to GIS implementation and its roll out to users within an organization is crucial for its long term assimilation. Depending on the contextual requirements, various implementation strategies exist spanning from the most revolutionary to the most evolutionary, which have an influence on the success of GIS projects and the realization of resulting business benefits within the central governments. This research compares between two strategies of GIS implementation within the Lebanese Municipalities. The first strategy is the “Technological Approach” which is focused on technology acquisition, overlaid on existing governmental frameworks. This approach gives minimal attention to capability building and the long term sustainability of the implemented program. The second strategy, referred to as the “Ecological Approach”, is naturally oriented to the function of the organization. This approach stresses on fostering the evolution of the program and on building the human capabilities. The Union of the Joumeh Municipalities will be presented as a case study under the “Ecological Approach” and the role of the GIS Center at the University of Balamand will be highlighted. Thus, this research contributes to the development of knowledge on technology implementation and the vital role of academia in the specific context of the Lebanese public sector so that this experience may pave the way for further applications.

Keywords: ecological approach GIS, low income countries, technological approach

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14174 Graph Similarity: Algebraic Model and Its Application to Nonuniform Signal Processing

Authors: Nileshkumar Vishnav, Aditya Tatu

Abstract:

A recent approach of representing graph signals and graph filters as polynomials is useful for graph signal processing. In this approach, the adjacency matrix plays pivotal role; instead of the more common approach involving graph-Laplacian. In this work, we follow the adjacency matrix based approach and corresponding algebraic signal model. We further expand the theory and introduce the concept of similarity of two graphs. The similarity of graphs is useful in that key properties (such as filter-response, algebra related to graph) get transferred from one graph to another. We demonstrate potential applications of the relation between two similar graphs, such as nonuniform filter design, DTMF detection and signal reconstruction.

Keywords: graph signal processing, algebraic signal processing, graph similarity, isospectral graphs, nonuniform signal processing

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14173 Towards a Competence Management Approach Based on Continuous Improvement

Authors: N. Sefiani, C. Fikri Benbrahim, A. Boumane, K. Reklaoui

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Nowadays, the reflection on competence management is the basic for new competitive strategies. It is considered as the core of the problems of the global supply chain. It interacts a variety of actors: information, physical and activities flows, etc. Even though competence management is seen as the key factor for any business success, the existing approaches demonstrate the deficiencies and limitations of the competence concept. This research has two objectives: The first is to make a contribution by focusing on the development of a competence approach, based on continuous improvement. It allows the enterprise to spot key competencies, mobilize them in order to serve its strategic objectives and to develop future competencies. The second is to propose a method to evaluate the level of Collective Competence. The approach was confirmed through an application carried out at an automotive company.

Keywords: competence, competencies’ approach, competence management, continuous improvement, collective competence level, performance indicator

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14172 A Theragnostic Approach for Alzheimer’s Disease Focused on Phosphorylated Tau

Authors: Tomás Sobrino, Lara García-Varela, Marta Aramburu-Núñez, Mónica Castro, Noemí Gómez-Lado, Mariña Rodríguez-Arrizabalaga, Antía Custodia, Juan Manuel Pías-Peleteiro, José Manuel Aldrey, Daniel Romaus-Sanjurjo, Ángeles Almeida, Pablo Aguiar, Alberto Ouro

Abstract:

Introduction: Alzheimer’s disease (AD) and other tauopathies are primary causes of dementia, causing progressive cognitive deterioration that entails serious repercussions for the patients' performance of daily tasks. Currently, there is no effective approach for the early diagnosis and treatment of AD and tauopathies. This study suggests a theragnostic approach based on the importance of phosphorylated tau protein (p-Tau) in the early pathophysiological processes of AD. We have developed a novel theragnostic monoclonal antibody (mAb) to provide both diagnostic and therapeutic effects. Methods/Results: We have developed a p-Tau mAb, which was doped with deferoxamine for radiolabeling with Zirconium-89 (89Zr) for PET imaging, as well as fluorescence dies for immunofluorescence assays. The p-Tau mAb was evaluated in vitro for toxicity by MTT assay, LDH activity, propidium iodide/Annexin V assay, caspase-3, and mitochondrial membrane potential (MMP) assay in both mouse endothelial cell line (bEnd.3) and cortical primary neurons cell cultures. Importantly, non-toxic effects (up to concentrations of p-Tau mAb greater than 100 ug/mL) were detected. In vivo experiments in the tauopathy model mice (PS19) show that the 89Zr-pTau-mAb and 89Zr-Fragments-pTau-mAb are stable in circulation for up to 10 days without toxic effects. However, only less than 0.2% reached the brain, so further strategies have to be designed for crossing the Brain-Blood-Barrier (BBB). Moreover, an intraparenchymal treatment strategy was carried out. The PS19 mice were operated to implement osmotic pumps (Alzet 1004) at two different times, at 4 and 7 months, to stimulate the controlled release for one month each of the B6 antibody or the IgG1 control antibody. We demonstrated that B6-treated mice maintained their motor and memory abilities significantly compared with IgG1 treatment. In addition, we observed a significant reduction in p-Tau deposits in the brain. Conclusions /Discussion: A theragnostic pTau-mAb was developed. Moreover, we demonstrated that our p-Tau mAb recognizes very-early pathology forms of p-Tau by non-invasive techniques, such as PET. In addition, p-Tau mAb has non-toxic effects, both in vitro and in vivo. Although the p-Tau mAb is stable in circulation, only 0.2% achieve the brain. However, direct intraventricular treatment significantly reduces cognitive impairment in Alzheimer's animal models, as well as the accumulation of toxic p-Tau species.

Keywords: alzheimer's disease, theragnosis, tau, PET, immunotherapy, tauopathies

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14171 Efficacy of Light-Emitting Diode-Mediated Photobiomodulation in Tendon Healing in a Murine Model

Authors: Sukwoong Kang

Abstract:

Background: The application of light-emitting diode (LED)-dependent photobiomodulation (PBM) in promoting post-tendon injury healing has been recently reported. Despite the establishment of a theoretical basis for ligament restoration through PBM, the lack of any empirical evidence deems this therapeutic strategy contentious. Therefore, the aim of this study was to investigate the potency of LED-based PBM in facilitating tendon healing in a murine model. Methods: Migration kinetics were analyzed at two specific wavelengths: 630 and 880 nm. The Achilles tendon in the hind limbs of Balb/c mice was severed via Achilles tendon transection. Subsequently, the mice were randomized into LED non-irradiation and LED irradiation groups. Mice with intact tendons were employed as healthy controls. The wounds were LED-irradiated for 20 min daily for two days. Histological properties, tendon healing mediators, and inflammatory mediators were screened on day 14. Results: The roundness of the nuclei and fiber structure, indicating the degree of infiltrated inflammatory cells and severity of fiber fragmentation, respectively, were considerably lower in the LED irradiation group than in the LED non-irradiation group. Immunohistochemical analysis depicted an increase in tenocytes (SCX+ cells) and a recovery of wounds with reduced fibrosis (lower collagen 3 and TGF-β1) in the LED irradiation group during healing; conversely, the LED non-irradiation group exhibited tissue fibrosis. The ratio of M2 macrophages to total macrophages was higher in the LED irradiation group than in the injured group. Conclusion: LED-based PBM in the Achilles tendon rupture murine model effectuated a rapid restoration of histological and immunochemical outcomes. The aforementioned findings suggest that LED-based PBM presents remarkable potential as an adjunct therapeutic for tendon healing and warrants further research to standardize various parameters to advance and establish it as a reliable treatment regime.

Keywords: photobiomodulation, light-emitting diode, tendon, regeneration

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14170 Differentially Expressed Protein Biomarkers in Early and Advanced Stage Young Triple-Negative Breast Cancer Patients

Authors: Shamim Mushtaq, Moazzam Shahid

Abstract:

Breast cancer (BC) claims the lives of half a million women every year and is the most common cause of death in the developing world. In 2019, it was estimated that BC alone accounts for 15% of all cancer deaths in younger women (aged < 45 years old) with advanced-stage lung metastasis. According to the World Health Organization & International Union against Cancer, in Asia, a high number of cancer-related deaths will be observed in 2020, whereas the burden will be reduced in Western countries due to awareness about the disease, better health facilities and advanced treatments. In the last 15 years, it has been reported that the incidence of BC has increased by 1.1% among Asian compared to the US population from 2003 to 2012. To date, several BC biological subtypes have been reported so far, which are associated with different treatment responses. The heterogeneity and diversity of BC reflected these different subtypes, including Luminal A (23.7% prevalence) and B (38.8% prevalence) that have pathological estrogen receptor (ER+)-positive tumors, the human epidermal growth factor receptor 2 (HER2) (11.2% prevalence) and triple-negative breast cancer (TNBC) (25% prevalence). According to Shaukat Khanum Memorial Cancer Hospital and Research Centre – Pakistan, ten years of data showed that among 636 BC patients, 30.5% had TNBC who were <40 years of age, which is an extremely alarming situation. Therefore, there is a dire need to explore and develop therapeutic targets for the treatment of early TNBC. Since the last decade, unfortunately, there has been little success in understanding the complexity of TNBC and in discovering new biological therapeutic targets. However, conventional chemotherapy is the only choice of treatment for TNBC patients. Many investigators revealed advances in multi-omics (multiple "omes", e.g., genome, proteome, transcriptome, epigenome, and microbiome) which were later identified as actionable targets and increased prevalence in TNBC patients. However, various drugs have been identified so far which are related to a particular diagnostic and prognostic biomarker. For example, Epidermal growth factor receptor ( EGFR or ErbB-1), HER-2/neu (ErbB-2), HER-3 (ErbB-3), and HER-4 (ErbB-4). Protein Transglin-2 (TAGLN 2 ) and Profilins-1 (Pfn-1 ) are the ubiquitously expressed large family of proteins present in all eukaryotes, enabling actin cytoskeletal reorganization. It is known that the oncogenic transformation of cells is accompanied by alteration in the actin cytoskeleton. There are causal connections between altered expression of actin cytoskeletal regulators and cancer progression. Our case-control study identified TAGLN-2 and Pfn-1 proteins in TNBC blood by mass spectrometry. Both TAGLN-2 and Pfn-1 proteins are differentially expressed in early and advanced stages of TNBS patients, which could be potential predictors or therapeutic targets for TNBC.

Keywords: TNBC, blood biomarkers, mass spectrometry, qPCR, ELISA

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14169 Biomimetic Strategies to Design Non-Toxic Antimicrobial Textiles

Authors: Isabel Gouveia

Abstract:

Antimicrobial textile materials may significantly reduce the risk of infections and because they are able to absorb substances from the skin and release therapeutic compounds to the skin, they can also find applications as complementary therapy of skin-diseases as part of standard management. Although functional textiles may be a promising area in skin disease/injury management, as part of standard management, few offer complementary treatment even though they are well known to reduce scratching and aiding emollient absorption, reducing infection, and alleviating pruritus. The reason for this may rely on the low quality of supporting evidence and negative effect that antimicrobial agents may exert on skin microbiome, as for example additional irritation of the vulnerable skin, and by causing resistant bacteria. Several antimicrobial agents have been tested in textiles: quaternary ammonium compounds, silver, polyhexamethylene-biguanides and triclosan have been used, with success. They have powerful bactericidal activity but the majority have a reduce spectrum of microbial inhibition and may cause skin irritation, ecotoxicity and bacteria resistance. Furthermore, the rising flow of strains resistant to last-resort antibiotics rekindles interest in alternative strategies. In this regard, new functional textiles incorporating highly specific antimicrobial agents towards pathogenic bacteria, are required. Recent research has been conducted on naturally occurring antimicrobials as novel alternatives to antibiotics. Conscious of this need our team firstly reported new approaches using L-cysteine and antimicrobial peptides (AMP). Briefly, we were able to develop different immobilization processes towards 6 Log Reduction against bacteria such as S. aureus and K. pneumoniae. Therefore, here we present several innovative antimicrobial textiles incorporating AMP and L-Cysteine which may open new avenues for the medical textiles market and biomaterials in general. Team references will be discussed as an overview and for comparison purposes in terms of potential therapeutic applications.

Keywords: Antimicrobials, Antimicrobial Textiles, Biomedical Textiles, Biomimetic surface functionalization

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14168 Neuro-Fuzzy Based Model for Phrase Level Emotion Understanding

Authors: Vadivel Ayyasamy

Abstract:

The present approach deals with the identification of Emotions and classification of Emotional patterns at Phrase-level with respect to Positive and Negative Orientation. The proposed approach considers emotion triggered terms, its co-occurrence terms and also associated sentences for recognizing emotions. The proposed approach uses Part of Speech Tagging and Emotion Actifiers for classification. Here sentence patterns are broken into phrases and Neuro-Fuzzy model is used to classify which results in 16 patterns of emotional phrases. Suitable intensities are assigned for capturing the degree of emotion contents that exist in semantics of patterns. These emotional phrases are assigned weights which supports in deciding the Positive and Negative Orientation of emotions. The approach uses web documents for experimental purpose and the proposed classification approach performs well and achieves good F-Scores.

Keywords: emotions, sentences, phrases, classification, patterns, fuzzy, positive orientation, negative orientation

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14167 The Use of Phototherapy with Unusual Case Studies in Counselling

Authors: Briar Schulz

Abstract:

The use of phototherapy within the counselling room offers significant advantages in extending far beyond typical "talk therapy" avenues. The benefits of using this approach are numerous and include: efficiency in recalling pertinent information in addition to utilizing a visual lens that often captures opulent detail that can be eluded in traditional dialogue. The goal of this presentation is to provide conference attendees with an opportunity to understand the therapeutic benefits and creative possibilities of incorporating photography into the clinical counselling process. This includes practical strategies for using in specific case studies, where studies of phototherapy have previously been limited. Ethical considerations and limitations to the process will also be addressed. Attendees will observe the benefits of using phototherapy with six longitudinal case studies including: a 30 year old female, with anorexia nervosa; a 22 year old self-harming individual with obsessive compulsive disorder; a 24 year old client with developmental delays, and bipolar disorder; a 14 year old client with Autism; and two clients with rare medical conditions struggling with depression and anxiety, one 21 years old and the other 16 years old. Aspects of each case will be linked to various theoretical modalities to highlight the efficiency and benefits of phototherapy in drawing important clinical conclusions. Furthermore, the use of phototherapy within these clinical areas remains a relatively unexplored area of the literature, and possibilities for future research will be highlighted. Finally, conference attendees will have the opportunity to try various phototherapy strategies within the interactive portion of this presentation. .

Keywords: Atypical, Case studies, Phototherapy, Photovoice

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14166 Survey of the Role of Contextualism in the Designing of Cultural Constructions Based on Rapoport Views

Authors: E. Zarei, M. Bazaei, A. Seifi, A. Keshavarzi

Abstract:

Amos Rapoport, based on his anthropology approach, believed that the space origins from the human body and influences on human body mutually. As a holistic approach in architecture, Contextualism describes a collection of views in philosophy which emphasize the context in which an action, utterance, or expression occurs, and argues that, in some important respect, the action, utterance, or expression can only be understood relative to that context. In this approach, the main goal – studying the role of cultural component in the Contextualism construction shaping up, based on Amos Rapoport’s anthropology approach- has being done by descriptive- analytic method. The results of the research indicate that in the field of Contextualism designing, referring to the cultural aspects are as necessary as the physical dimensions of a construction. Rapoport believes that the shape of a construction is influenced by cultural aspects and he suggests a kind of mutual interaction between human and environment that should be considered in housing. The mail goal of contextual architecture is to establish an interaction between environment, human and culture. According to this approach, a desirable design should be in harmony with this approach.

Keywords: Amos Rapoport, anthropology, contextual architecture, culture

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14165 From User's Requirements to UML Class Diagram

Authors: Zeineb Ben Azzouz, Wahiba Ben Abdessalem Karaa

Abstract:

The automated extraction of UML class diagram from natural language requirements is a highly challenging task. Many approaches, frameworks and tools have been presented in this field. Nonetheless, the experiments of these tools have shown that there is no approach that can work best all the time. In this context, we propose a new accurate approach to facilitate the automatic mapping from textual requirements to UML class diagram. Our new approach integrates the best properties of statistical Natural Language Processing (NLP) techniques to reduce ambiguity when analysing natural language requirements text. In addition, our approach follows the best practices defined by conceptual modelling experts to determine some patterns indispensable for the extraction of basic elements and concepts of the class diagram. Once the relevant information of class diagram is captured, a XMI document is generated and imported with a CASE tool to build the corresponding UML class diagram.

Keywords: class diagram, user’s requirements, XMI, software engineering

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14164 Effects of Pulsed Electromagnetic and Static Magnetic Fields on Musculoskeletal Low Back Pain: A Systematic Review Approach

Authors: Mohammad Javaherian, Siamak Bashardoust Tajali, Monavvar Hadizadeh

Abstract:

Objective: This systematic review study was conducted to evaluate the effects of Pulsed Electromagnetic (PEMF) and Static Magnetic Fields (SMG) on pain relief and functional improvement in patients with musculoskeletal Low Back Pain (LBP). Methods: Seven electronic databases were searched by two researchers independently to identify the published Randomized Controlled Trials (RCTs) on the efficacy of pulsed electromagnetic, static magnetic, and therapeutic nuclear magnetic fields. The identified databases for systematic search were Ovid Medline®, Ovid Cochrane RCTs and Reviews, PubMed, Web of Science, Cochrane Library, CINAHL, and EMBASE from 1968 to February 2016. The relevant keywords were selected by Mesh. After initial search and finding relevant manuscripts, all references in selected studies were searched to identify second hand possible manuscripts. The published RCTs in English would be included to the study if they reported changes on pain and/or functional disability following application of magnetic fields on chronic musculoskeletal low back pain. All studies with surgical patients, patients with pelvic pain, and combination of other treatment techniques such as acupuncture or diathermy were excluded. The identified studies were critically appraised and the data were extracted independently by two raters (M.J and S.B.T). Probable disagreements were resolved through discussion between raters. Results: In total, 1505 abstracts were found following the initial electronic search. The abstracts were reviewed to identify potentially relevant manuscripts. Seventeen possibly appropriate studies were retrieved in full-text of which 48 were excluded after reviewing their full-texts. Ten selected articles were categorized into three subgroups: PEMF (6 articles), SMF (3 articles), and therapeutic nuclear magnetic fields (tNMF) (1 article). Since one study evaluated tNMF, we had to exclude it. In the PEMF group, one study of acute LBP did not show significant positive results and the majority of the other five studies on Chronic Low Back Pain (CLBP) indicated its efficacy on pain relief and functional improvement, but one study with the lowest sessions (6 sessions during 2 weeks) did not report a significant difference between treatment and control groups. In the SMF subgroup, two articles reported near significant pain reduction without any functional improvement although more studies are needed. Conclusion: The PEMFs with a strength of 5 to 150 G or 0.1 to 0.3 G and a frequency of 5 to 64 Hz or sweep 7 to 7KHz can be considered as an effective modality in pain relief and functional improvement in patients with chronic low back pain, but there is not enough evidence to confirm their effectiveness in acute low back pain. To achieve the appropriate effectiveness, it is suggested to perform this treatment modality 20 minutes per day for at least 9 sessions. SMFs have not been reported to be substantially effective in decreasing pain or improving the function in chronic low back pain. More studies are necessary to achieve more reliable results.

Keywords: pulsed electromagnetic field, static magnetic field, magnetotherapy, low back pain

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14163 Thyroid Malignancy Concurrent with Hyperthyroidism: Variations with Thyroid Status and Age

Authors: N. J. Nawarathna, N. R. Kmarasinghe, D. Chandrasekara, B. M. R. S. Balasooriya, R. A. A. Shaminda, R. J. K. Senevirathne

Abstract:

Introduction: Thyroid malignancy associated with hyperthyroidism is considered rare. Retrospective studies have shown the incidence of thyroid malignancy in hyperthyroid patients to be low (0.7-8.5%). To assess the clinical relevance of this association, thyroid status in a cohort of patients with thyroid malignancy were analyzed. Method: Thyroid malignancies diagnosed histologically in 56 patients, over a 18 month period beginning from April 2013, in a single surgical unit at Teaching Hospital Kandy were included. Preoperative patient details and progression of thyroid status were asessed with Thyroid Stimulating Hormone, free Thyroxin and free Triiodothyronine levels. Results: Amongst 56 patients Papillary carcinoma was diagnosed in 44(78.6%), follicular carcinomas in 7(12.5%) and 5(8.9%) with medullary and anaplastic carcinomas. 12(21.4%) were males and 44(78.6%) were females. 20(35.7%) were less than 40years, 29(51.8%) were between 40 to 59years and 7(12.5%) were above 59years. Cross tabulation of Type of carcinoma with Gender revealed likelihood ratio of 6.908, Significance p = 0.032. Biochemically 12(21.4%) were hyperthyroid. Out of them 5(41.7%) had primary hyperthyroidism and 7(58.3%) had secondary hyperthyroidism. Mean age of euthyroid patients was 43.77years (SD 10.574) and hyperthyroid patients was 53.25years(SD 16.057). Independent Samples Test t is -2.446, two tailed significance p =0.018. When cross tabulate thyroid status with Age group Likelihood Ratio was 9.640, Significance p = 0.008. Conclusion: Papillary carcinoma is seen more among females. Among the patients with thyroid carcinomas, those with biochemically proven hyperthyroidism were more among the older age group than those who were euthyroid. Hence careful evaluation of elderly hyperthyroid patients to select the most suitable therapeutic approach is justified.

Keywords: age, hyperthyroidism, thyroid malignancy, thyroid status

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14162 Using Gene Expression Programming in Learning Process of Rough Neural Networks

Authors: Sanaa Rashed Abdallah, Yasser F. Hassan

Abstract:

The paper will introduce an approach where a rough sets, gene expression programming and rough neural networks are used cooperatively for learning and classification support. The Objective of gene expression programming rough neural networks (GEP-RNN) approach is to obtain new classified data with minimum error in training and testing process. Starting point of gene expression programming rough neural networks (GEP-RNN) approach is an information system and the output from this approach is a structure of rough neural networks which is including the weights and thresholds with minimum classification error.

Keywords: rough sets, gene expression programming, rough neural networks, classification

Procedia PDF Downloads 357
14161 Measuring the Economic Impact of Cultural Heritage: Comparative Analysis of the Multiplier Approach and the Value Chain Approach

Authors: Nina Ponikvar, Katja Zajc Kejžar

Abstract:

While the positive impacts of heritage on a broad societal spectrum have long been recognized and measured, the economic effects of the heritage sector are often less visible and frequently underestimated. At macro level, economic effects are usually studied based on one of the two mainstream approach, i.e. either the multiplier approach or the value chain approach. Consequently, there is limited comparability of the empirical results due to the use of different methodological approach in the literature. Furthermore, it is also not clear on which criteria the used approach was selected. Our aim is to bring the attention to the difference in the scope of effects that are encompassed by the two most frequent methodological approaches to valuation of economic effects of cultural heritage on macroeconomic level, i.e. the multiplier approach and the value chain approach. We show that while the multiplier approach provides a systematic, theory-based view of economic impacts but requires more data and analysis, the value chain approach has less solid theoretical foundations and depends on the availability of appropriate data to identify the contribution of cultural heritage to other sectors. We conclude that the multiplier approach underestimates the economic impact of cultural heritage, mainly due to the narrow definition of cultural heritage in the statistical classification and the inability to identify part of the contribution of cultural heritage that is hidden in other sectors. Yet it is not possible to clearly determine whether the value chain method overestimates or underestimates the actual economic impact of cultural heritage since there is a risk that the direct effects are overestimated and double counted, but not all indirect and induced effects are considered. Accordingly, these two approaches are not substitutes but rather complementary. Consequently, a direct comparison of the estimated impacts is not possible and should not be done due to the different scope. To illustrate the difference of the impact assessment of the cultural heritage, we apply both approaches to the case of Slovenia in the 2015-2022 period and measure the economic impact of cultural heritage sector in terms of turnover, gross value added and employment. The empirical results clearly show that the estimation of the economic impact of a sector using the multiplier approach is more conservative, while the estimates based on value added capture a much broader range of impacts. According to the multiplier approach, each euro in cultural heritage sector generates an additional 0.14 euros in indirect effects and an additional 0.44 euros in induced effects. Based on the value-added approach, the indirect economic effect of the “narrow” heritage sectors is amplified by the impact of cultural heritage activities on other sectors. Accordingly, every euro of sales and every euro of gross value added in the cultural heritage sector generates approximately 6 euros of sales and 4 to 5 euros of value added in other sectors. In addition, each employee in the cultural heritage sector is linked to 4 to 5 jobs in other sectors.

Keywords: economic value of cultural heritage, multiplier approach, value chain approach, indirect effects, slovenia

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14160 Self-Organization-Based Approach for Embedded Real-Time System Design

Authors: S. S. Bendib, L. W. Mouss, S. Kalla

Abstract:

This paper proposes a self-organization-based approach for real-time systems design. The addressed issue is the mapping of an application onto an architecture of heterogeneous processors while optimizing both makespan and reliability. Since this problem is NP-hard, a heuristic algorithm is used to obtain efficiently approximate solutions. The proposed approach takes into consideration the quality as well as the diversity of solutions. Indeed, an alternate treatment of the two objectives allows to produce solutions of good quality while a self-organization approach based on the neighborhood structure is used to reorganize solutions and consequently to enhance their diversity. Produced solutions make different compromises between the makespan and the reliability giving the user the possibility to select the solution suited to his (her) needs.

Keywords: embedded real-time systems design, makespan, reliability, self-organization, compromises

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14159 Bridge Healthcare Access Gap with Artifical Intelligence

Authors: Moshmi Sangavarapu

Abstract:

The US healthcare industry has undergone tremendous digital transformation in recent years, but critical care access to lower-income ethnicities is still in its nascency. This population has historically showcased substantial hesitation to seek any medical assistance. While the lack of sufficient financial resources plays a critical role, the existing cultural and knowledge barriers also contribute significantly to widening the access gap. It is imperative to break these barriers to ensure timely access to therapeutic procedures that can save important lives! Based on ongoing research, healthcare access barriers can be best addressed by tapping the untapped potential of caregiver communities first. They play a critical role in patients’ diagnoses, building healthcare knowledge and instilling confidence in required therapeutic procedures. Recent technological advancements have opened many avenues by developing smart ways of reaching the large caregiver community. A digitized go-to-market strategy featuring connected media coupled with smart IoT devices and geo-location targeting can be collectively leveraged to reach this key audience group. AI/ML algorithms can be thoroughly trained to identify relevant data signals from users' location and browsing behavior and determine useful marketing touchpoints. The web behavior can be further assimilated with natural language processing to identify contextually relevant interest topics and decipher potential caregivers on digital avenues to serve that brand message. In conclusion, grasping the true health access journey of any lower-income ethnic group is important to design beneficial touchpoints that can alleviate patients’ concerns and allow them to break their own access barriers and opt for timely and quality healthcare.

Keywords: healthcare access, market access, diversity barriers, patient journey

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14158 Wound Healing Potential and Comparison of Mummy Substance Effect on Adipose and Wharton’s Jelly-Derived Mesenchymal Stem Cells Co-Cultured with Human Fibroblast

Authors: Sepideh Hassanpour Khodaei

Abstract:

Background/Objectives: The purpose of this study is to evaluate the effect of mummy substances on two issues of proliferation and production of matrix protein synthesis in wound healing. Methods: The methodology used for this aim involves isolating mesenchymal stem cells and human fibroblasts procured at Pastor Institute, Iran. The cells were treated with mummy substances separately and co-cultured between ASCs and WJSCs, and fibroblasts. Proliferation was assessed by Ki67 method in monolayer conditions. Synthesis of components of extracellular matrix (ECM) such as collagen type I, type III, and fibronectin 1 (FN1) was determined by qPCR. Results: The effects of adipocyte stem cells (ASCs), Wharton Jelly Stem Cells (WJSCs), and Mummy material on fibroblast proliferation and migration were evaluated. The present finding underlined the importance of Mummy material, ASCs, and WJSCs in the proliferation and migration of fibroblast cells. Furthermore, the expression of collagen I, III, and FN1 was increased in the presence of the above material and cells. Conclusion: This study presented an effective in vitro method for the healing process. Hence, the prospect of utilizing Mummy material and stem cell-based therapies in wound healing as a therapeutic approach is promising.

Keywords: mummy material, wound healing, adipose tissue, Wharton’s jelly

Procedia PDF Downloads 92