Search results for: combined therapy

Authors: Ovidiu Vlaicu, Leontina Banica, Dan Otelea, Andrei-Jose Petrescu, Costin-Ioan Popescu

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Hepatitis C Virus (HCV) infects 170 million peoples worldwide. Major advances have been made recently in HCV standard of care with interferon-free therapy being already approved. Despite major progress in HCV therapy, the genotype associated treatment efficacy and toxicity still represent issues to address. To identify endogenous factors involved in different stages of HCV life cycle, we have developed a trans-packaging system for HCV subgenomic replicons lacking core protein gene. Huh7 cells were used to generate a packaging cell line expressing the core protein in an inducible manner. The core packaging cell line was able to trans-complemented various subgenomic replicons to secret infectious trans-complemented HCV particles (HCV-TCP). Further, we constructed subgenomic replicons with foreign epitopes suitable for immunoaffinity purification or fluorescence microscopy studies. We have shown that the insertion has not effects on the efficacy of trans-complementation yielding similar titers to the control subgenomic replicon. This system will be a valuable tool in studying pre- and post-assembly events in HCV life cycle and for the fast identification of HCV assembly inhibitors.

Keywords: assembly inhibitors, core protein, HCV, trans-complementation

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Authors: Sanaa Mekdad, Leenah Alsayed

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Pharmacists play an important role in the CDTM in the care of patients with heart failure (HF). CDTM allows specialized, dedicated clinical pharmacists in a formal agreement in collaborative practice with physicians. Thus, the aim of this study is to investigate the role of cardiology clinical pharmacists in CDTM in decreasing hospitalization and cost. We studied patients with left ventricular systolic dysfunction in a cluster-randomized selection in a tertiary care center. We allocated 296 patients to pharmacist intervention from 1480 patients. Results: With an acceptance rate of 86%, we documented 696 interventions carried out by clinical pharmacists in cardiology. The average intervention was 2.4 patients, and the admission after interventions decreased from 0.79 to. 0.24 (p value = 0.001). Conclusions: In HF CDTM, clinical pharmacists play a crucial role in enhancing medication management, patient education, and lifestyle modification of patients with chronic heart failure. These efforts improve patients' outcomes and lower costs by reducing hospitalization and other associated expenses.

Keywords: cardiology, medication management, heart failure, outpatient therapy, pharmacist-based services, chronic heart failure, heart failure recommendations, CDTM, Middle East, pharmacist-based services, quality of life, pharmacist

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Authors: Saeed Dehnavi, Zahra Dehnavi

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Background: Psychodrama, as a form of art therapy, helps people to enact and use role-plays for a specific problem, rather than just talking about it, in an effort to review the problem, gain feedback from group members, find appropriate solutions, and practice them for their life. This paper evaluated the effectiveness of psychodrama on enhancing self-esteem of young adolescent boys. Methodology: This is aquasi-experimental research study, using a pre-post testing plan with control group.From four secondary schools in Kermanshah – Iran, 210 adolescent boys (aged 13 and 14 years) were asked to complete Koper Smith's self-esteem measure scale. Given the low self-esteem scores (less than the cut-off of 23), a number of 20 individuals were selected and randomly placed into two control and experimental groups. The experimental group participated in a twelve-session psychodrama therapy plan for 6 weeks, while the control group received no intervention. Data analysis was carried out by the analysis of covariance (ANCOVA). Results: The results of ANCOVA analysis showed an increase in the post-test scores for self-esteem, and such increase was statistically significant. Conclusion: The findings indicated the effectiveness of psychodrama on self-esteem enhancement of young boys. During psychodrama sessions, the adolescents learned to take the initiative, communicate with others in an excited state, and improve their self-esteem with positive and constructive experiences.

Keywords: psychodrama, self-esteem, young adolescents, boys

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Authors: Ahmed Mohamed El-Shamy, Akram Abbas El-Awady, Mahmoud Taha Eldestawy

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Background: The present study was to evaluate clinically and radiographically the combined effect of split crest technique by ultrasonic bone surgery and platelet concentrates in implant site development. Methods: Forty patients with narrow ridge were participated in this study. Patients were assigned randomly into one of the following four groups according to treatment: Group 1: Patients received split-crest technique by ultrasonic bone surgery with implant placement. Group 2: Patients received split-crest technique by ultrasonic bone surgery with implant placement and PRF. Group 3: Patients received split-crest technique by ultrasonic bone surgery with implant placement and PRP. Group 4: Patients received split-crest technique by ultrasonic bone surgery with implant placement and collagen membrane. Modified plaque index, modified sulcus bleeding index, and implant stability were recorded as a baseline and measured again at 3 and 6 months. CBCT scans were taken immediately after surgery completion and at 9 months to evaluate bone density at the bone-implant interface. Results after 6 months; collagen group showed statistically significantly lower mean modified bleeding index than the other groups. After 3 months, the PRF group showed statistically significantly higher mean implant stability with ostell ISQ units' than the other groups. After 6 months, the PRF group showed statistically significantly higher mean implant stability with ostell ISQ units' than the other groups. After 6 months, the PRF group showed statistically significantly higher mean bone density than the collagen group. Conclusion: Ultrasonic bone surgery in split-crest technique can be a successful option for increasing implant stability values throughout the healing period. The use of a combined technique of ultrasonic bone surgery with PRF and simultaneous implant placement potentially improves osseointegration (bone density). PRF membranes represent advanced technology for the stimulation and acceleration of bone regeneration.

Keywords: dental implants, split-crest, PRF, PRP

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Authors: Djalal Boualili

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This article considers the problem of sizing prime movers for combined heating and power (CHP) systems operating at full load to satisfy a fraction of a facility's electric load, i.e. a base load. Prime mover sizing is examined using three criteria: operational cost, carbon dioxide emissions (CDE), and primary energy consumption (PEC). The sizing process leads to consider ratios of conversion factors applied to imported electricity to conversion factors applied to fuel consumed. These ratios are labelled RCost, R CDE, R PEC depending on whether the conversion factors are associated with operational cost, CDE, or PEC, respectively. Analytical results show that in order to achieve savings in operational cost, CDE, or PEC, the ratios must be larger than a unique constant R Min that only depends on the CHP components efficiencies. Savings in operational cost, CDE, or PEC due to CHP operation are explicitly formulated using simple equations. This facilitates the process of comparing the tradeoffs of optimizing the savings of one criterion over the other two – a task that has traditionally been accomplished through computer simulations. A hospital building, located in Chlef, Algeria, was used as an example to apply the methodology presented in this article.

Keywords: sizing, heating and power, ratios, energy consumption, carbon dioxide emissions

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Authors: Khalid A. Salman, Shereen Wagih, Tariq Munshi, Musaed Almalki, Safwan Zatari, Zahid Khan

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Aim: To measure exposure levels to family members and caregivers of Saudi patients treated with low dose I131 therapy, and household radiation exposure rate to predict different factors that can affect radiation exposure. Patients and methods: All adult self dependent patients with hyperthyroidism or cancer thyroid referred for low dose radioactive I131 therapy on outpatient basis are included. Radiation protection procedures are given to the participant and family members in details. TLD’s were dispensed to each participant in sufficient quantity for his/her family members living in the household. TLD’s are collected at fifth days post-dispense from patients who agreed to have a home visit during which the household is inspected and level of radiation contamination of surfaces was measured. Results: Thirty-two patients were enrolled in the current study, with a mean age of 43.1± 17.1 years Out of them 25 patients (78%) are females. I131 therapy was given in twenty patients (63%) for cancer thyroid of and for toxic goiter in the remaining twelve patients (37%), with an overall mean I131 dose of 24.1 ± 7.5mCi that is relatively higher in the former. The overall number of household family members and helpers of patients are 139, out of them77 are females (55.4%) & 62 are males (44.6%) with a mean age of 29.8± 17.6. The mean period of contact with the patient is 7.6 ±5.6hours. The cumulative radiation exposure shows that radiation exposure to all family members is below the exposure constraint (1mSv), with a range of 109 to 503uSv, and a mean value of 220.9±91 uSv. Numerical data shows a little higher exposure rate for family members of those who receive higher dose of I131 (patients with thyroid cancer) and household members who spent longer time with the patient, yet, the difference is statistically insignificant (P>0.05). Besides, no significant correlation was found between the degree of cumulative exposure of the family members to their gender, age, socioeconomic standard, educational level and residential factors. In the 21 home visits all data from bedrooms, reception areas and kitchens are below hazardous limits (0.5uSv/h) apart from bathrooms that give a slightly higher reading of 0.57±0.39 uSv/h in those with cancer thyroid who receive a higher radiation dose. A statistically significant difference was found between radiation exposure rate in bathrooms used by the patient versus those used by family members only, with a mean value of exposure rate of 0.701±0.21 uSv/h and 0.17±0.82 uSv/h respectively, with a p-value of 0.018 (<0.05). Conclusion: Family members of patients treated with low dose I131 on outpatient basis have a good compliance to radiation protection instruction if given properly with a cumulative radiation exposure rate evidently beyond the radiation exposure constraints of 1 mSv. Given I131 dose, hours spent with the patient, age, gender, socioeconomic standard, educational level and residential factors have no significant correlation with the cumulative radiation exposure. The patient bathroom exhibits more radiation exposure rate, needing more strict instructions for patient bathroom use and health hygiene.

Keywords: family members, radiation exposure, radioactive iodine therapy, radiation safety

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Authors: Krittiya Pornmai, Sumaeth Chavadej

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The increasing in global energy demand has affected the climate change caused by the generation of greenhouse gases. Therefore, the objective of this work was to investigate a direct production of synthesis gas from a CO₂-containing natural gas by using gliding arc discharge plasma technology. In this research, the effects of steam reforming, combined steam reforming and partial oxidation, and using multistage gliding arc discharge system on the process performance have been discussed. The simulated natural gas used in this study contains 70% methane, 5% ethane, 5% propane, and 20% carbon dioxide. In comparison with different plasma reforming processes (under their optimum conditions), the steam reforming provides the highest H₂ selectivity resulting from the cracking reaction of steam. In addition, the combined steam reforming and partial oxidation process gives a very high CO production implying that the addition of both oxygen and steam can offer the acceptably highest synthesis gas production. The stage number of plasma reactor plays an important role in the improvement of CO₂ conversion. Moreover, 3 stage number of plasma reactor is considered as an optimum stage number for the reforming of CO₂-containing natural gas with steam and partial oxidation in term of providing low energy consumption as compared with other plasma reforming processes.

Keywords: natural gas, reforming process, gliding arc discharge, plasma technology

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Authors: Ahmed Mohamed Nasr, Waseim Ragab Azzam, Nada Osama Ramadan

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Contaminated soil can weaken the stability of buildings and infrastructure, posing serious risks to their structural integrity. Therefore, this study aims to understand how oil contamination affects the torsion behavior of model steel piles at different soil densities. This research is crucial for evaluating the structural integrity and stability of piles in oil-contaminated environments. Clean sand samples and heavy motor oil were mixed in amounts ranging from 0 to 6% of the soil's dry weight. The mixture was thoroughly mixed to ensure uniform distribution of the oil throughout the sandy soil for simulating the field conditions. In these investigations, the relative densities (Dr), pile slenderness ratio (Lp/Dp), oil content (O.C%), and contaminated sand layer thickness (LC) were all different. Also, the paper presents an analysis of piles that are loaded both vertically and torsionally. The findings demonstrated that the pre-applied torsion load led to a decrease in the vertical bearing ability of the pile. Also, at Dr = 80%, the ultimate vertical load under combined load at constant torsional load T = (1/3Tu, 2/3Tu, and Tu) in the cases of (Lc/Lp) = 0.5 and (Lp/Dp) =13.3 was found to be reduced by (1.48, 2.78, and 4.15%) less than piles under independent vertical load, respectively so it is crucial to consider the torsion load during pile design.

Keywords: torsion-vertical load, oil-contaminated sand, twist angle, steel pile

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Authors: Naser Shagerdi Esmaeli, Mohsen Hamidpour

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Purposes: The activation of coagulation in patients with cancer contributes significantly to morbidity and mortality rates and may play a fundamental role in the host response to growing tumor’s. Patients with cancer are clearly at high risk for the development of venous thromboembolism (VTE), particularly during chemotherapy and surgery. This situation is aggravated by the use of venous access catheters and possibly growth factors. Methods: Data derived from large, randomized, controlled trials have been used to determine the true incidence of this complication of cancer and its treatment. The incidence based on the analyses of these randomized controlled trials varies from 1% for limited stage patients with breast cancer treated with tamoxifen to 60% for patients with any type of cancer who are subjected to orthopedic surgery and do not receive prophylactic therapy. Results: In view of the morbidity and mortality attributable to VTE in cancer, widespread utilization of prophylactic anticoagulation therapy, which has proven safe and effective in a variety of situations, should be considered. While migratory thrombophlebitis is a clear indicator of an underlying neoplasm, the risk of cancer in patients with the more typical form of VTE has been the subject of intense debate over recent years. Conclusion: Some investigators have suggested that the relative risk of being diagnosed with occult cancer within six months of an episode of VTE (particularly recurrent VTE) could be up to 10-fold. However, the cost-effectiveness of aggressive screening for cancer in patients with VTE has not yet been defined adequately.

Keywords: venous thromboembolism, malignancy, cancer, tumor, heparin

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Authors: Sadeem Aljamaan, Reem Hariri, Rahaf Alghamdi, Batool Alotaibi, Batool Alsenan, Lama Althunayyan, Areej Alnemer

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The aim of this study is to correlate between radiological findings and histopathological results in regard to the breast imaging-reporting and data system scores, size of breast masses, molecular subtypes and suspicious radiological features, as well as to assess the concordance rate in histological grade between core biopsy and surgical excision among breast cancer patients, followed by analyzing the change of concordance rate in relation to neoadjuvant chemotherapy in a Saudi population. A retrospective review was conducted over 6-year period (2017-2022) on all breast core biopsies of women preceded by radiological investigation. Chi-squared test (χ2) was performed on qualitative data, the Mann-Whitney test for quantitative non-parametric variables, and the Kappa test for grade agreement. A total of 641 cases were included. Ultrasound, mammography, and magnetic resonance imaging demonstrated diagnostic accuracies of 85%, 77.9% and 86.9%; respectively. magnetic resonance imaging manifested the highest sensitivity (72.2%), and the lowest was for ultrasound (61%). Concordance in tumor size with final excisions was best in magnetic resonance imaging, while mammography demonstrated a higher tendency of overestimation (41.9%), and ultrasound showed the highest underestimation (67.7%). The association between basal-like molecular subtypes and the breast imaging-reporting and data system score 5 classifications was statistically significant only for magnetic resonance imaging (p=0.04). Luminal subtypes demonstrated a significantly higher percentage of speculation in mammography. Breast imaging-reporting and data system score 4 manifested a substantial number of benign pathologies in all the 3 modalities. A fair concordance rate (k= 0.212 & 0.379) was demonstrated between excision and the preceding core biopsy grading with and without neoadjuvant therapy, respectively. The results demonstrated a down-grading in cases post-neoadjuvant therapy. In cases who did not receive neoadjuvant therapy, underestimation of tumor grade in biopsy was evident. In summary, magnetic resonance imaging had the highest sensitivity, specificity, positive predictive value and accuracy of both diagnosis and estimation of tumor size. Mammography demonstrated better sensitivity than ultrasound and had the highest negative predictive value, but ultrasound had better specificity, positive predictive value and accuracy. Therefore, the combination of different modalities is advantageous. The concordance rate of core biopsy grading with excision was not impacted by neoadjuvant therapy.

Keywords: breast cancer, mammography, MRI, neoadjuvant, pathology, US

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Authors: Solomon Huluka, Akrum Abdul-Latif, Rachid Baleh

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Metal foams have been developed intensively as a new class of materials for the last two decades due to their unique structural and multifunctional properties. The aim of this experimental work was to characterize the effect of biaxial loading complexity (combined compression-torsion) on the plastic response of highly uniform architecture open-cell aluminum foams of spherical porous with a density of 80%. For foam manufacturing, the Kelvin cells model was used to generate the generally spherical shape with a cell diameter of 11 mm. A patented rig called ACTP (Absorption par Compression-Torsion Plastique), was used to investigate the foam response under quasi-static complex loading paths having different torsional components (i.e. 0°, 45° and 60°). The key mechanical responses to be examined are yield stress, stress plateau, and energy absorption capacity. The collapse mode was also investigated. It was concluded that the higher the loading complexity, the greater the yield strength and the greater energy absorption capacity of the foam. Experimentally, it was also noticed that there were large softening effects that occurred after the first pick stress for both biaxial-45° and biaxial-60° loading.

Keywords: aluminum foam, loading complexity, characterization, biaxial loading

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Authors: Mahmoud Nadir, Adel Ghenaiet

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The main purpose of this study is the thermodynamic modeling, the parametric analysis, and the optimization of three pressure level reheat HRSG (Heat Recovery Steam Generator) using PSO method (Particle Swarm Optimization). In this paper, a parametric analysis followed by a thermodynamic optimization is presented. The chosen objective function is the specific work of the steam cycle that may be, in the case of combined cycle (CC), a good criterion of thermodynamic performance analysis, contrary to the conventional steam turbines in which the thermal efficiency could be also an important criterion. The technologic constraints such as maximal steam cycle temperature, minimal steam fraction at steam turbine outlet, maximal steam pressure, minimal stack temperature, minimal pinch point, and maximal superheater effectiveness are also considered. The parametric analyses permitted to understand the effect of design parameters and the constraints on steam cycle specific work variation. PSO algorithm was used successfully in HRSG optimization, knowing that the achieved results are in accordance with those of the previous studies in which genetic algorithms were used. Moreover, this method is easy to implement comparing with the other methods.

Keywords: combined cycle, HRSG thermodynamic modeling, optimization, PSO, steam cycle specific work

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Authors: Ahmedou Moulaye Idriss, Tfeil Yahya, Tamas Ungi, Gabor Fichtinger

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Image-guided therapy (IGT) plays a crucial role in minimally invasive procedures for liver interventions. Accurate segmentation of the liver and precise needle placement is essential for successful interventions such as needle aspiration. In this study, we propose a deep learning-based liver 3D slicer designed to enhance segmentation accuracy and facilitate needle aspiration procedures. The developed 3D slicer leverages state-of-the-art convolutional neural networks (CNNs) for automatic liver segmentation in medical images. The CNN model is trained on a diverse dataset of liver images obtained from various imaging modalities, including computed tomography (CT) and magnetic resonance imaging (MRI). The trained model demonstrates robust performance in accurately delineating liver boundaries, even in cases with anatomical variations and pathological conditions. Furthermore, the 3D slicer integrates advanced image registration techniques to ensure accurate alignment of preoperative images with real-time interventional imaging. This alignment enhances the precision of needle placement during aspiration procedures, minimizing the risk of complications and improving overall intervention outcomes. To validate the efficacy of the proposed deep learning-based 3D slicer, a comprehensive evaluation is conducted using a dataset of clinical cases. Quantitative metrics, including the Dice similarity coefficient and Hausdorff distance, are employed to assess the accuracy of liver segmentation. Additionally, the performance of the 3D slicer in guiding needle aspiration procedures is evaluated through simulated and clinical interventions. Preliminary results demonstrate the effectiveness of the developed 3D slicer in achieving accurate liver segmentation and guiding needle aspiration procedures with high precision. The integration of deep learning techniques into the IGT workflow shows great promise for enhancing the efficiency and safety of liver interventions, ultimately contributing to improved patient outcomes.

Keywords: deep learning, liver segmentation, 3D slicer, image guided therapy, needle aspiration

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Authors: Vijaya Madhuri Devraj, Swarnalatha Guditi, Kiran Kumar Bokara, Gangadhar Taduri

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Cell-based strategies may open therapeutic approaches that promote tolerance through manipulation of macrophages to increase long-term transplant survival rates and minimize side effects of the current immune suppressive regimens. The aim of the present study was, therefore, to test and compare the therapeutic potential of MSC and Tregs on macrophage polarization to develop an alternate cell-based treatment option in kidney transplantation. In the current protocol, macrophages from kidney transplant recipients with graft dysfunction were co-cultured with MSCs and Treg cells with and without cell-cell contact on transwell plates, further to quantitatively assess macrophage polarization in response to MSC and Treg treatment over time, M1 and M2 cell surface markers were used. Additionally, multiple soluble analytes were analyzed in cell supernatant by using bead-based immunoassays. Furthermore, to confirm our findings, gene expression analysis was done. MSCs induced the formation of M2 macrophages more than Tregs when macrophages M0 were cultured in transwell without cell contact. From this, we deduced the mechanism that soluble factors present in the MSCs condition media are involved in skewing of macrophages towards type 2 macrophages; similarly, in co-culture with cell-cell contact, MSCs resulted in more M2 type macrophages than Tregs. And an important finding of this study is the combination of both MSC-Treg showed significantly effective and consistent results in both with and without cell contact setups. Hence, it is suggestive to prefer MSCs over Tregs for secretome-based therapy and a combination of both for either therapy for effective transplantation outcomes. Our findings underline a key role of Tregs and MSCs in promoting macrophage polarization towards anti-inflammatory type. The study has great importance in prolongation of allograft and patient survival without any rejection by cell-based therapy, which induce self-tolerance and controlling infection.

Keywords: graft rejection, graft tolerance, macrophage polarization, mesenchymal stem cells, regulatory T cells, transplant immunology

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Authors: S. Chockalingam, U. Natarajan, D. M. Santhoshsarang

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Particle damping is a promising vibration attenuating technique in boring tool than other type of damping with minimal effect on the strength, rigidity and stiffness ratio of the machine tool structure. Due to the cantilever nature of boring tool holder in operations, it suffers chatter when the slenderness ratio of the tool gets increased. In this study, Copper-Stainless steel (SS) particles were packed inside the boring tool which acts as a damper. Damper suppresses chatter generated during machining and also improves the machining efficiency of the tool with better slenderness ratio. In the first approach of particle damping, combined Cu-SS particles were packed inside the vibrating tool, whereas Copper and Stainless steel particles were selected separately and packed inside another tool and their effectiveness was analysed in this simulation. This study reveals that the efficiency of finite element simulation of the boring tools when equipped with particles such as copper, stainless steel and a combination of both. In this study, the newly modified boring tool holder with particle damping was simulated using ANSYS12.0 with and without particles. The aim of this study is to enhance the structural rigidity through particle damping thus avoiding the occurrence of resonance in the boring tool during machining.

Keywords: boring bar, copper-stainless steel, chatter, particle damping

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Authors: Heiko Jessen, Laura Tanus, Slobodan Ruzicic

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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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Authors: Yang Yang, Luciana Magalhães Rebelo Alencar, Martha Sahylí Ortega Pijeira, Beatriz da Silva Batista, Alefe Roger Silva França, Erick Rafael Dias Rates, Ruana Cardoso Lima, Sara Gemini-Piperni, Ralph Santos-Oliveira

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Radium-²²³ dichloride ([²²³Rₐ]RₐCl₂) is an alpha particle-emitting radiopharmaceutical currently approved for the treatment of patients with castration-resistant prostate cancer, symptomatic bone metastases, and no known visceral metastatic disease. [²²³Rₐ]RₐCl₂ is bone-seeking calcium mimetic that bonds into the newly formed bone stroma, especially osteoblastic or sclerotic metastases, killing the tumor cells by inducing DNA breaks in a potent and localized manner. Nonetheless, the successful therapy of osteosarcoma as primary bone tumors is still a challenge. Nanomicelles are colloidal nanosystems widely used in drug development to improve blood circulation time, bioavailability, and specificity of therapeutic agents, among other applications. In addition, the enhanced permeability and retention effect of the nanosystems, and the renal excretion of the nanomicelles reported in most cases so far, are very attractive to achieve selective and increased accumulation in tumor site as well as to increase the safety of [²²³Rₐ]RₐCl₂ in the clinical routine. In the present work, [²²³Rₐ]RₐCl₂ nanomicelles were produced, characterized, in vitro evaluated, and compared with pure [²²³Rₐ]RₐCl2 solution using SAOS2 osteosarcoma cells. The [²²³Rₐ]RₐCl₂ nanomicelles were prepared using the amphiphilic copolymer Pluronic F127. The dynamic light scattering analysis of freshly produced [²²³Rₐ]RₐCl₂ nanomicelles demonstrated a mean size of 129.4 nm with a polydispersity index (PDI) of 0.303. After one week stored in the refrigerator, the mean size of the [²²³Rₐ]RₐCl₂ nanomicelles increased to 169.4 with a PDI of 0.381. Atomic force microscopy analysis of [223Rₐ]RₐCl₂ nanomicelles exhibited spherical structures whose heights reach 1 µm, suggesting the filling of 127-Pluronic nanomicelles with [²²³Rₐ]RₐCl₂. The viability assay with [²²³Rₐ]RₐCl₂ nanomicelles displayed a dose-dependent response as it was observed using pure [²²³Rₐ]RₐCl2. However, at the same dose, [²²³Rₐ]RₐCl₂ nanomicelles were 20% higher efficient in killing SAOS2 cells when compared with pure [²²³Rₐ]RₐCl₂. These findings demonstrated the effectiveness of the nanosystem validating the application of nanotechnology in targeted alpha therapy with [²²³Ra]RₐCl₂. In addition, the [²²³Rₐ]RaCl₂nanomicelles may be decorated and incorporated with a great variety of agents and compounds (e.g., monoclonal antibodies, aptamers, peptides) to overcome the limited use of [²²³Ra]RₐCl₂.

Keywords: nanomicelles, osteosarcoma, radium dichloride, targeted alpha therapy

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Authors: Shuo Li, Yannick Coffinier, Chann Lagadec, Fabrizio Cleri, Katsuhiko Nishiguchi, Akira Fujiwara, Soo Hyeon Kim, Nicolas Clément

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The need for single cell detection and analysis techniques has increased in the past decades because of the heterogeneity of individual living cells, which increases the complexity of the pathogenesis of malignant tumors. In the search for early cancer detection, high-precision medicine and therapy, the technologies most used today for sensitive detection of target analytes and monitoring the variation of these species are mainly including two types. One is based on the identification of molecular differences at the single-cell level, such as flow cytometry, fluorescence-activated cell sorting, next generation proteomics, lipidomic studies, another is based on capturing or detecting single tumor cells from fresh or fixed primary tumors and metastatic tissues, and rare circulating tumors cells (CTCs) from blood or bone marrow, for example, dielectrophoresis technique, microfluidic based microposts chip, electrochemical (EC) approach. Compared to other methods, EC sensors have the merits of easy operation, high sensitivity, and portability. However, despite various demonstrations of low limits of detection (LOD), including aptamer sensors, arrayed EC sensors for detecting single-cell have not been demonstrated. In this work, a new technique based on 20-nm-thick nanopillars array to support cells and keep them at ideal recognition distance for redox-labeled aptamers grafted on the surface. The key advantages of this technology are not only to suppress the false positive signal arising from the pressure exerted by all (including non-target) cells pushing on the aptamers by downward force but also to stabilize the aptamer at the ideal hairpin configuration thanks to a confinement effect. With the first implementation of this technique, a LOD of 13 cells (with5.4 μL of cell suspension) was estimated. In further, the nanosupported cell technology using redox-labeled aptasensors has been pushed forward and fully integrated into a single-cell electrochemical aptasensor array. To reach this goal, the LOD has been reduced by more than one order of magnitude by suppressing parasitic capacitive electrochemical signals by minimizing the sensor area and localizing the cells. Statistical analysis at the single-cell level is demonstrated for the recognition of cancer cells. The future of this technology is discussed, and the potential for scaling over millions of electrodes, thus pushing further integration at sub-cellular level, is highlighted. Despite several demonstrations of electrochemical devices with LOD of 1 cell/mL, the implementation of single-cell bioelectrochemical sensor arrays has remained elusive due to their challenging implementation at a large scale. Here, the introduced nanopillar array technology combined with redox-labeled aptamers targeting epithelial cell adhesion molecule (EpCAM) is perfectly suited for such implementation. Combining nanopillar arrays with microwells determined for single cell trapping directly on the sensor surface, single target cells are successfully detected and analyzed. This first implementation of a single-cell electrochemical aptasensor array based on Brownian-fluctuating redox species opens new opportunities for large-scale implementation and statistical analysis of early cancer diagnosis and cancer therapy in clinical settings.

Keywords: bioelectrochemistry, aptasensors, single-cell, nanopillars

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Authors: A. Zeynolabedin, M. A. Olyaei, B. Ghiasi

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Drought is an inevitable part of the earth’s climate. It occurs regularly with no clear warning and without recognizing borders. In addition, its impact is cumulative and not immediately discernible. Iran is located in a semi-arid region where droughts occur periodically as natural hazard. Standardized Precipitation Index (SPI), Surface Water Supply Index (SWSI), and Palmer Drought Severity Index (PDSI) are three well-known indices which describe drought severity; each has its own advantages and disadvantages and can be used for specific types of drought. These indices take into account some factors such as precipitation, reservoir storage and discharge, temperature, and potential evapotranspiration in determining drought severity. In this paper, first all three indices are calculated in Aharchay river watershed located in northwestern part of Iran in East Azarbaijan province. Next, based on two other important parameters which are groundwater level and solar radiation, two new indices are defined. Finally, considering all five aforementioned indices, a combined drought index (CDI) is presented and calculated for the region. This combined index is based on all the meteorological, hydrological, and agricultural features of the region. The results show that the most severe drought condition in Aharchay watershed happened in Jun, 2004. The result of this study can be used for monitoring drought and prepare for the drought mitigation planning.

Keywords: drought, GIS, intensity index, regional assessment, variation maps

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Authors: Rylle Evan Gabriel Zamora, Micah Dennise Malia, Abygail Deniese Villabona

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The primary motivators of altruism are usually viewed as mutually exclusive. In this study, we wanted to know if the two primary motivators, reciprocity and empathy, can work together in motivating altruism. Therefore, we wanted to find out if there is a significant interaction of effects between reciprocity and empathy. To show how this may occur, we devised the combined altruism model, which is based on Batson’s empathy altruism hypothesis. A sample of 120, 6th-grade students were randomly selected and then randomly assigned to four treatment groups. A 2x2 between subjects’ design was used, which had empathy and reciprocity as independent variables, and altruism as the dependent variable. The study made use of materials that were effort based, where subjects were required to complete a task or a puzzle to help a person in a given scenario, two videos, one to prime empathy were also used. This along with Witt & Boleman’s adapted Self-Reported Altruism Scale was used to determine an individual’s altruism. It was found that both variables were significant in motivating altruism, with empathy being the greater of the two. However, there was no significant interaction of effects between the two variables. To explain why this occurred, we turned to the combined altruism model, where it was found that when empathically primed, we tend to not think of ourselves when helping others. Future studies could focus on other variables, especially age which is said to be one of the greatest factors that influenced the results of the experiment.

Keywords: reciprocity, empathy, altruism, experimental psychology, social psychology

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Authors: Arshad Munir, Naseem Akhtar

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The determination of the Sufi is to effort towards unity. His main purpose is to bring humanity, separated as it is into so many different units, closer together in the deeper understanding of life. His mission is to bring about brotherhood among races, nations and faiths and to respect one another's faith, scripture and teacher. Sufi is to confer sympathy on these lives, to impart love, compassion and kindheartedness on all creations. The Sufi message is the resonance of the same Divine message which has always come and will always come to inform humanity. It is the continuation of all the pronounced religions which have come at several times and it is amalgamation of them all, which was the wish of all the prophets. Pakistan, who came into being in the name of Islam unfortunately, have linked with terrorism. It is a disgrace that in contemporary day Pakistan, mullahism and the recent cancer of Talibanisation are gradually eating into what had kept us integral as a society. Terrorism has grown-up to develop a prime safety pressure to the area. The terrorism has deadly caused decrease in overseas and local investment, exports, physical infrastructure, and wealth stock ultimately leading to damage of the socio-economic status of Pakistan. Main reasons are ignorance about the actual teaching of Islam both by Muslim and non-Muslim, exploitation by the religious and political influential, sectarianism and extremism, lack of tolerance and broadmindedness and reaction and retortion by the sufferer. The key treatment and therapy of the abovementioned illnesses exist in the messages of Sufism.

Keywords: sufism, love, Pakistan, terrorism

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Authors: Kalpana Singh, Nikita Katiyar

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This research investigates the impact of Raga Bhairavi, a prominent musical scale in Indian classical music, on the mood and basic physiological parameters of research scholars at the University of Lucknow - India. The study focuses on the potential therapeutic effects of listening to Raga Bhairavi during morning hours. A controlled experimental design is employed, utilizing self-reporting tools for mood assessment and monitoring physiological indicators such as heart rate, oxygen saturation levels, body temperature and blood pressure. The hypothesis posits that exposure to Raga Bhairavi will lead to positive mood modulation and a reduction in physiological stress markers among research scholars. Data collection involves pre and post-exposure measurements, providing insights into the immediate and cumulative effects of the musical intervention. The study aims to contribute valuable information to the growing field of music therapy, offering a potential avenue for enhancing the well-being and productivity of individuals engaged in intense cognitive activities. Results may have implications for the integration of music-based interventions in academic and research environments, fostering a conducive atmosphere for intellectual pursuits.

Keywords: bio-musicology, classical music, mood assessment, music therapy, physiology, Raga Bhairavi

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Authors: Huseyn Nuraddin Qurbanov

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The reliable food supply of the population of the republic is one of the main directions of the state's economic policy. Grain growing, which is the basis of agriculture, is important in this area. In the cultivation of cereals on the slopes, the application of equal amounts of mineral fertilizers the under the soil before sowing is a very important technological process. The low level of technical equipment in this area prevents producers from providing the country with the necessary quality cereals. Experience in the operation of modern technical means has shown that, at present, there is a need to provide an equal amount of fertilizer on the slopes to under the soil, fully meeting the agro-technical requirements. No fundamental changes have been made to the industrial machines that fertilize the under the soil, and unequal application of fertilizers under the soil on the slopes has been applied. This technological process leads to the destruction of new seedlings and reduced productivity due to intolerance to frost during the winter for the plant planted in the fall. In special climatic conditions, there is an optimal fertilization rate for each agricultural product. The application of fertilizers to the soil is one of the conditions that increase their efficiency in the field. As can be seen, the development of a new technical proposal for fertilizing and plowing the slopes in equal amounts on the slopes, improving the technological and design parameters, and taking into account the physical and mechanical properties of fertilizers is very important. Taking into account the above-mentioned issues, a combined plough was developed in our laboratory. Combined plough carries out pre-sowing technological operation in the cultivation of cereals, providing a smooth equal amount of mineral fertilizers under the soil on the slopes. Mathematical models of a smooth spreader that evenly distributes fertilizers in the field have been developed. Thus, diagrams and graphs obtained without distribution on the 8 partitions of the smooth spreader are constructed under the inclined angles of the slopes. Percentage and productivity of equal distribution in the field were noted by practical and theoretical analysis.

Keywords: combined plough, mineral fertilizer, equal sowing, fertilizer norm, grain-crops, sowing fertilizer

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Authors: Akhilesh G. Naik, Dipankar Pal

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In today’s scenario, the complexity of digital signal processing (DSP) applications and various microcontroller architectures have been increasing to such an extent that the traditional approaches to multiplier design in most processors are becoming outdated for being comparatively slow. Modern processing applications require suitable pipelined approaches, and therefore, algorithms that are friendlier with pipelined architectures. Traditional algorithms like Wallace Tree, Radix-4 Booth, Radix-8 Booth, Dadda architectures have been proven to be comparatively slow for pipelined architectures. These architectures, therefore, need to be optimized or combined with other architectures amongst them to enhance its performances and to be made suitable for pipelined hardware/architectures. Recently, Vedic algorithm mathematically has proven to be efficient by appearing to be less complex and with fewer steps for its output establishment and have assumed renewed importance. This paper describes and shows how the Vedic algorithm can be better suited for pipelined architectures and also can be combined with traditional architectures and algorithms for enhancing its ability even further. In this paper, we also established that for complex applications on DSP and other microcontroller architectures, using Vedic approach for multiplication proves to be the best available and efficient option.

Keywords: Wallace Tree, Radix-4 Booth, Radix-8 Booth, Dadda, Vedic, Single-Stage Karatsuba (SSK), Looped Karatsuba (LK)

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Authors: Alvin Saputra, Felix Wijovi

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Background: Adults with Autism Spectrum Disorder (ASD) often experience emotional dysregulation and heightened suicidality. Dialectical Behavior Therapy (DBT) and Radically Open DBT (RO-DBT) have shown promise in addressing these challenges, though research on their effectiveness in ASD populations remains limited. This systematic review aims to evaluate the impact of DBT and RO-DBT on emotional regulation, depression, and suicidality in adults with ASD. Methods: A systematic review was conducted by searching databases such as PubMed, PsycINFO, and Scopus for studies published on DBT and RO-DBT interventions in adults with Autism Spectrum Disorder (ASD). Inclusion criteria were peer-reviewed studies that reported on emotional regulation, suicidality, or depression outcomes. Data extraction focused on sample characteristics, intervention details, and outcome measures. Quality assessment was performed using standard systematic review criteria to ensure reliability and relevance of findings. Results: 4 studies comprising a total of 343 participants were included in this study. DBT and RO-DBT interventions demonstrated a medium effect size (Cohen's d = 0.53) in improving emotional regulation for adults with ASD, with ASD participants achieving significantly better outcomes than non-ASD individuals. RO-DBT was particularly effective in reducing maladaptive overcontrol, though high attrition and a predominantly White British sample limited generalizability. At end-of-treatment, DBT significantly reduced suicidal ideation (z = −2.24; p = 0.025) and suicide attempts (z = −3.15; p = 0.002) compared to treatment as usual (TAU), although this effect did not sustain at 12 months. Depression severity decreased with DBT (z = −1.99; p = 0.046), maintaining significance at follow-up (z = −2.46; p = 0.014). No significant effects were observed for social anxiety, and two suicides occurred in the TAU group. Conclusions: DBT and RO-DBT show potential efficacy in reducing emotional dysregulation, suicidality, and depression in adults with ASD, though the effects on suicidality may diminish over time. High dropout rates and limited sample diversity suggest further research is needed to confirm long-term benefits and improve applicability across broader populations.

Keywords: dialectical behaviour therapy, emotional dysregulation, autism spectrum disorder, suicidality

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Authors: Delphine Morales, Florian Lombart, Agathe Truchot, Pauline Maire, Pascale Vigneron, Antoine Galmiche, Catherine Lok, Muriel Vayssade

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Targeted therapy molecules are used as a first-line treatment for metastatic melanoma with B-Raf mutation. Nevertheless, these molecules can cause side effects to patients and are efficient on 50 to 60 % of them. Indeed, melanoma cell sensitivity to targeted therapy molecules is dependent on tumor microenvironment (cell-cell and cell-extracellular matrix interactions). To better unravel factors modulating cell sensitivity to B-Raf inhibitor, we have developed and compared several melanoma models: from metastatic melanoma cells cultured as monolayer (2D) to a co-culture in a 3D dermal equivalent. Cell response was studied in different melanoma cell lines such as SK-MEL-28 (mutant B-Raf (V600E), sensitive to Vemurafenib), SK-MEL-3 (mutant B-Raf (V600E), resistant to Vemurafenib) and a primary culture of dermal human fibroblasts (HDFn). Assays have initially been performed in a monolayer cell culture (2D), then a second time on a 3D dermal equivalent (dermal human fibroblasts embedded in a collagen gel). All cell lines were treated with Vemurafenib (a B-Raf inhibitor) for 48 hours at various concentrations. Cell sensitivity to treatment was assessed under various aspects: Cell proliferation (cell counting, EdU incorporation, MTS assay), MAPK signaling pathway analysis (Western-Blotting), Apoptosis (TUNEL), Cytokine release (IL-6, IL-1α, HGF, TGF-β, TNF-α) upon Vemurafenib treatment (ELISA) and histology for 3D models. In 2D configuration, the inhibitory effect of Vemurafenib on cell proliferation was confirmed on SK-MEL-28 cells (IC50=0.5 µM), and not on the SK-MEL-3 cell line. No apoptotic signal was detected in SK-MEL-28-treated cells, suggesting a cytostatic effect of the Vemurafenib rather than a cytotoxic one. The inhibition of SK-MEL-28 cell proliferation upon treatment was correlated with a strong expression decrease of phosphorylated proteins involved in the MAPK pathway (ERK, MEK, and AKT/PKB). Vemurafenib (from 5 µM to 10 µM) also slowed down HDFn proliferation, whatever cell culture configuration (monolayer or 3D dermal equivalent). SK-MEL-28 cells cultured in the dermal equivalent were still sensitive to high Vemurafenib concentrations. To better characterize all cell population impacts (melanoma cells, dermal fibroblasts) on Vemurafenib efficacy, cytokine release is being studied in 2D and 3D models. We have successfully developed and validated a relevant 3D model, mimicking cutaneous metastatic melanoma and tumor microenvironment. This 3D melanoma model will become more complex by adding a third cell population, keratinocytes, allowing us to characterize the epidermis influence on the melanoma cell sensitivity to Vemurafenib. In the long run, the establishment of more relevant 3D melanoma models with patients’ cells might be useful for personalized therapy development. The authors would like to thank the Picardie region and the European Regional Development Fund (ERDF) 2014/2020 for the funding of this work and Oise committee of "La ligue contre le cancer".

Keywords: 3D human skin model, melanoma, tissue engineering, vemurafenib efficiency

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Authors: Rudinë Fetahaj, Flaka Isufi, Kristina Hansson

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While evidence shows that in most European countries’ multilingualism is rising, unfortunately, the focus of Speech and Language Therapy (SLT) is still monolingualism. Furthermore, there is sparse information on how the needs of multilingual children with language disorders such as Developmental Language Disorder (DLD) are being met and which factors affect the intervention approach of SLTs when treating DLD. This study aims to examine the relationship and correlation between the number of languages SLTs speak, years of experience, and length of education with the advice they give to parents of multilingual children with DLD regarding which language to be spoken. This is a cross-sectional study where a survey was completed online by 2608 SLTs across Europe and data has been used from a 2017 COST-action project. IBM-SPSS-28 was used where descriptive analysis, correlation and Kruskal-Wallis test were performed.SLTs mainly advise the parents of multilingual children with DLD to speak their native language at home. Besides years of experience, language status and the level of education showed to have no association with the type of advice SLTs give. Results showed a non-significant moderate positive correlation between SLTs years of experience and their advice regarding the native language, whereas language status and length of education showed no correlation with the advice SLTs give to parents.

Keywords: quantitative study, developmental language disorders, multilingualism, speech and language therapy, children, European context

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Authors: Radwa R. El-Saadany , Medhat Abu Zeid, Tarek Omar, Marwa S. Maqsoud

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Attention deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders characterized by attention deficit, hyperactivity, and impulsivity. Neurofeedback (NF) is one of the neurotherapy treatments that cause brain wave changes. Method: The current pseudo-experimental study with a pre–post-test design was conducted on a population of children with attention deficit hyperactivity disorder (ADHD).The sample size comprised of (30) children selected by random sampling method and assigned to two therapeutic groups: First therapeutic group received a neurofeedback program. Based on QEEG, it reached (10) children. The second therapeutic group received an organization skills training program, it reached (10) and the control group that did not receive programs, it reached (10) children. Results: There are significant differences between pre- and post-assessments among therapeutic groups in reducing the three core symptoms of ADHD in favor of post measurement. There are no significant differences between post-assessment and follow up measurement of the therapeutic groups.

Keywords: QEEG-based neurofeedback therapy program, organizational skills training program, attention deficit hyperactivity disorder

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Authors: K. R. Thabethe, G. A. Adefolaju, M. J. Hosie

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Cervical cancer is the third most commonly diagnosed cancer globally and it is one of three AIDS defining malignancies. Highly active antiretroviral therapy (HAART) is a combination of three or more antiretroviral drugs and has been shown to play a significant role in reducing the incidence of some AIDS defining malignancies, although its effect on cervical cancer is still unclear. The aim of this study was to investigate the relationship between cervical cancer and HAART. This was achieved by studying the expression of two signalling molecules expressed in cervical cancer; MUC1 and P65. Following the 24 hour treatment of a cervical cancer cell line, HCS-2, with drugs which are commonly used as part of HAART at their clinical plasma concentrations, real-time qPCR and immunofluorescence were used in order to study gene and protein expression. A one way ANOVA followed by a Tukey Kramer Post Hoc test was conducted using JMP 11 software on both sets of data. The drug classified as a protease inhibitor (PI) (i.e. LPV/r) reduced MUC1 and P65 gene and protein expression more than the other drug tested. PIs are known to play a significant role in cell death, therefore the cells were thought to be more susceptible to cell death following treatment with PIs. In conclusion, the drugs used, especially the PI showed some anticancer effects by facilitating cell death through decreased gene and protein expression of MUC1 and P65 and present promising agents for cancer treatment.

Keywords: cervical cancer, haart, MUC1, P65

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Authors: Pello Alfonso-Muniozguren, Madeleine Bussemaker, Devendra Saroj, Judy Lee

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Wastewater treatment is becoming a worldwide concern due to new and tighter environmental regulations, and the increasing need for fresh water for the exponentially growing population. The meat industry has one of the highest consumption of water producing up to 10 times more polluted (BOD) wastewaters in comparison to domestic sewage. Therefore, suitable wastewater treatment methods are required to ensure the wastewater quality meet regulations before discharge. In the present study, a combined lab scale activated sludge-sonication system was used to treat pre-treated abattoir wastewater. A hydraulic retention time of 24 hours and a solid retention time of 13 days were used for the activated sludge process and using ultrasound as tertiary treatment. Different ultrasonic frequencies, powers and sonication times were applied to the samples and results were analysed for chemical oxygen demand (COD), biological oxygen demand (BOD), total suspended solids, pH, total coliforms and total viable counts. Additionally, both mechanical and chemical effects of ultrasound were quantified for organic matter removal (COD and BOD) and disinfection (microorganism inactivation) using different techniques such as aluminum foil pitting, flow cytometry, and KI dosimetry.

Keywords: abattoir wastewater, ultrasound, wastewater treatment, water disinfection

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