Search results for: Sabri Çolak

Authors: Giti Sabri, Sohrab Imani, Ali Ahadiyat, Aref Maroof, Yahya Ostadi

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Recently, there has been a growing interest in research concerning the possible use of plant extracts as alternatives to synthetic insecticides. In this research, the insecticidal effects of Carum copticum essential oils against rice weevil adults were investigated in laboratory condition. Essential oils was extracted through distillation with water using Clevenger apparatus. Tests of randomized complete block included six concentrations and three replications for essential oils (fumigant toxicity) along with control treatment in condition of 27±1ºC degrees Celsius temperature, relative humidity of 65 ± 5 percent and darkness. LC50 values were calculated by SPSS.21.0 software which presented the value of LC50 of Carum copticum essential oils after 48 hurs, 187.35± 0.40 µl/l air on rice weevil adults. Results showed that increasing the concentration of essential oils increased the mortality rate cases. The results also showed that essential oils of Carum copticum are effective biological sources which can effectively protect stored grain from infestation by the rice weevil; although for application of these combinations further research may be needed.

Keywords: insecticidial effects, essential oil, Carum copticum, Sitophilus oryzae

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Authors: Pirzada Sami Ullah Sabri

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The present study examines the relationship between work engagement (WE) and employee turnover intentions (TI) in telecommunication sector using human resource development climate (HRDC) as a moderator. Based on 538 employees of telecommunication sector Hierarchal regression analysis is employed to examine the influence of HRDC on the relationship of work engagement and turnover intentions. The result indicates the negative correlation between work engagement and turnover intentions; HRD climate support as a powerful moderator increases the work engagement and lessens the turnover intentions. The study shows the importance of favorable and supportive HRD climate which foster the work engagement of the employees in the organization. By understanding the importance of human resource development climate and work engagement in reducing the turnover intentions can increase the productivity and performance of the organization.

Keywords: turnover intentions, work engagement, human resource development, climate, hierarchal regression analysis, telecommunication sector

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Authors: Fatma Zehra Engin Sagirli, Eyup Sabri Kayali, A. Sezai Sarac

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In this study, Poly (acrylonitrile-co-methylacrylate)/N-Methyl Pyrrole and Pyrrole ([P(AN-co-MA)]-NMPy and [P(AN-co-MA)]-PPy) core–shell nanoparticles were obtained by in situ emulsion polymerization in the presence of Sodium dodecyl benzene sulfonate and sodium dodecyl sulfate (SDBS and SDS) by using ammonium per sulphate in the aqueous medium. The spectroscopic characterizations during the formation of nanocomposites were studied using Attenuated total reflectance Fourier transform infrared (FTIR-ATR) spectroscopy, ultraviolet–visible spectrophotometer (Uv-Vis). Electrical conductivity of the emulsion solution was measured by Conductivity Meter from aqueous sample solution. Also, yield of the powder nanocomposites was measured. SDBS and SDS used for investigation of surfactant effect on yield, electrical conductivity and polymerization process. Determination of polymerization yield, (FTIR-ATR) and (Uv-Vis) prove that the SDBS surfactant become more incorporated into the conducting polymers and there is strong interaction between the [P(AN-co-MA)]-PPy derivatives which prepared by these surfactants. The similar inclusion of SDS into conducting polymers was not observed, there is a remarkable difference at nanocomposites which prepared with SDS.

Keywords: nanocomposites, core-shell, pyrole, surfactant

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Authors: Burcu Babadağ Savaş, Nihal Orlu, Güler Balcı Alparslan, Ertuğrul Çolak, Cengiz Korkmaz

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Introduction/objectives: We aimed to investigate the effect of humor on pain and state anxiety in patients with rheumatoid arthritis (RA) receiving biologic intravenous (IV) infusion therapy. Method: The study sample consisted of 36 patients who met the classification criteria for RA and inclusion criteria in a rheumatology outpatient clinic at a university hospital between September 2020 and November 2021. Two sample groups were formed: the intervention group (watching a comedy movie) (n=18) and the control group (n=18). The intervention group consisted of the patient watching a comedy movie of his/her choice from an archive created by the researchers during the biological IV infusion therapy (approximately 90-120 minutes). The data collection instruments used before and after the test were the descriptive identification form, the visual analog scale (VAS), and the state anxiety scale. Results: The mean VAS scores of patients in the intervention group were 5.05 ± 2.01 in the pre-test and 2.61 ± 1.91 in the post-test. The mean state anxiety scores of patients in the intervention group were 45.94 ± 9.97 in the pre-test and 34.22 ± 6.57 in the post-test. Thus, patients who watched comedy movies during biologic IV infusion therapy in the infusion center had a greater reduction in pain scores than the control group and the effect size was small. Although there was a decrease in state anxiety scores in both groups, there was no significant difference between groups and the effect size was not relevant. Conclusions: During IV infusion therapy, watching comedy movies is recommended as a nursing care intervention for reducing pain in patients with RA in cooperation with other health professionals.

Keywords: watching comedy movie, humor, pain, anxiety, nursing, care

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Authors: Izani Uzair Zubair, Mohd Ismail Ibrahim, Mohd Nazri Shafei, Hassan Merican Omar Naina Merican, Mohamad Sabri Othman, Mohd Izmi Ahmad Ibrahim, Rasilah Ramli, Rajpal Singh Karam Singh

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Nurses experience a higher prevalence of low back pain (LBP) and musculoskeletal complaints as compared to other hospital workers. Due to no proper policy related to LBP, the job has exposed them to the problem. Thus, the current study aims to look at the intensity of the problem and factors associated with development of LBP. Method and Tools: A cross sectional study was carried out among 1292 nurses from six public hospitals in Penang. They were randomly selected and those who were pregnant and have been diagnosed to have LBP were excluded. A Malay validated BACK Questionnaire was used. The associated factors were determined by using multiple logistic regression from SPSS version 20.0. Result: Most of the respondents were at mean age 30 years old and had mean working experience 86 months. The prevalence of LBP was identified as 76% (95% CI 74, 82). Factors that were associated with LBP among nurses include lifting a heavy object (OR2.626 (95% CI 1.978, 3.486) p =0.001 and the estimation weight of the lifted object (OR1.443 (95% CI 1.056, 1.970) p =0.021. Conclusion: Nurses who practice lifting heavy object and weight of the object lifted give a significant contribution to the development of LBP. The prevalence of the problem is significantly high. Thus, a proper no weight lifting policy should be considered.

Keywords: low back pain, nurses, Penang public hospital, Penang

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Authors: Sofiene Amara, Mohamed Ali Bahri, Sabri Gaied Chortane

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The purpose of this study was to examine the effect of personal goal setting on psychological parameters (cognitive anxiety, somatic anxiety, and self-confidence) and the 50m freestyle performance. 30 young swimmers participated in this investigation, and was divided into three groups, the first group (G1, n = 10, 14 ± 0.7 years old) was prepared for the competition without a fixed target (method 1), the second group (G2, n = 10, 14 ± 0.9 years old) was oriented towards a vague goal 'Do your best' (method 2), while the third group (G3, n = 10, 14 ± 0, 5 years old) was invited to answer a goal that is difficult to reach according to a goal-setting interval (GST) (method 3). According to the statistical data of the present investigation, the cognitive and somatic anxiety scores in G1 and G3 were higher than in G2 (G1-G2, G3-G2: cognitive anxiety, P = 0.000, somatic anxiety: P = 0.000 respectively). On the other hand, the self-confidence score was lower in G1 compared with the other two groups (G1-G2, G3-G2: P = 0.02, P = 0.03 respectively). Our assessment also shows that the 50m freestyle time performance was improved better by method 3 (pre and post-Test: P = 0.006, -2.5sec, 7.83%), than by method 2 (pre and Post-Test: P = 0.03; -1sec; 3.24%), while, performance remained unchanged in G1 (P > 0.05). To conclude, the setting of a difficult goal by GST is more effective to improve the chronometric performance in the 50m freestyle, but at the same time increased the values ​​of the cognitive and somatic anxiety. For this, the mental trainers and the staff technical, invited to develop models of mental preparation associated with this method of setting a goal to help swimmers on the psychological level.

Keywords: cognitive anxiety, goal setting, performance of swimming freestyle, self-confidence, somatic anxiety

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Authors: Sabri Mrayed, David Maccioni, Greg Leslie

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Seawater desalination has been accepted as one of the most effective solutions to the growing problem of a diminishing clean drinking water supply. Currently, two desalination technologies dominate the market – the thermally driven multi-stage flash distillation (MSF) and the membrane based reverse osmosis (RO). However, in recent years membrane distillation (MD) has emerged as a potential alternative to the established means of desalination. This research project intended to determine the viability of MD as an alternative process to MSF and RO for seawater desalination. Specifically the project involves conducting a thermodynamic analysis of the process based on the second law of thermodynamics to determine the efficiency of the MD. Data was obtained from experiments carried out on a laboratory rig. In order to determine exergy values required for the exergy analysis, two separate models were built in Engineering Equation Solver – the ’Minimum Separation Work Model’ and the ‘Stream Exergy Model’. The efficiency of MD process was found to be 17.3 %, and the energy consumption was determined to be 4.5 kWh to produce one cubic meter of fresh water. The results indicate MD has potential as a technique for seawater desalination compared to RO and MSF. However, it was shown that this was only the case if an alternate energy source such as green or waste energy was available to provide the thermal energy input to the process. If the process was required to power itself, it was shown to be highly inefficient and in no way thermodynamically viable as a commercial desalination process.

Keywords: desalination, exergy, membrane distillation, second law efficiency

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Authors: Sherif Sabri, Nael Samir, Mohamed Ali, Ahmed ElSakhawy

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Introduction: There is growing evidence to support the hypothesis that serum matrix metalloproteinase -9 in could be an early predictor of mortality in septic patients. Aim of the work: Study the relationship of matrix metalloproteinase 9 in patients with SIRS in comparison to septic patients in day 0 and day 2. Patients and Methods: This is a prospective observational study conducted on 40 adult critically ill patients staying more than 24 hours in ICU either surgical or medical department, El Fayoum General Hospital in the period from November 2014 to March 2015. Patients met at least two of the criteria for severe inflammatory response syndrome (SIRS). Diagnostic criteria include several clinical and laboratory findings of sepsis induced tissue hypoperfusion or organ dysfunction. Samples were grouped as drawn either at admission, or at day 2 after admission. Results: Patients were divided into two groups: The non-sepsis (SIRS) group, which included 15 (37.5%) patients with no later evidence of sepsis were enrolled as controls. The Sepsis group, which included 25 patients diagnosed to have SIRS with later evidence of sepsis with positive culture. Exploring serum level of MMP-9 in non-survivors and survivors, there was significant increase in non-survivors if compared to survivors at admission p-value 0.001 (mean value in survivors 4.4mg/dl±4.1mg/dl at admission versus mean value in non-survivors 11.9mg/dl±5.8mg/dl) and after two days of admission was also significant increase p-value 0.001 (mean value in survivors 10.9mg/dl ±9.4mg/dl versus mean value in non-survivors 22.6mg/dl±10.4). Conclusion: MMP-9 levels in septic patients have a beneficial role in ICU for high-risk stratification as it is an independent marker of mortality in severe sepsis.

Keywords: matrix metalloproteinase (MMP-9), sepsis, septic shock, systemic inflamatory response syndrome

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Authors: Ozen Asut, Gulifeiya Abuduxike, Imge Begendi, Mustafa O. Canatan, Merve Colak, Gizem Ozturk, Lara Tasan, Ahmed Waraiet, Songul A. Vaizoglu, Sanda Cali

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Obesity among children and adolescents is one of the critical public health problems worldwide. Internet addiction is one of the sedentary behaviors that cause obesity due to the excessive screen time and reduced physical activities. We aimed to examine the relationships between the screen time, internet addiction and other lifestyle behaviors with obesity among high school students in the Near East College in Nicosia, Northern Cyprus. A cross-sectional study conducted among 469 secondary school students, mean age 11.95 (SD, 0.81) years. A self-administrated questionnaire was applied to assess the screen time and lifestyle behaviors. The Turkish adopted version of short-form of internet addiction test was used to assess internet addiction problems. Height and weight were measured to calculate BMI and classified based on the BMI percentiles for sex and age. Descriptive analysis, Chi-Square test, and multivariate regression analysis were done. Of all, 17.2% of the participants were overweight and obese, and 18.1% had internet addictions, while 40.7% of them reported having screen time more than two hours. After adjusting the analysis for age and sex, eating snacks while watching television (OR, 3.04; 95% CI, 1.28-7.21), self- perceived body weight (OR, 24.9; 95% CI, 9.64-64.25) and having a play station in the room (OR, 4.6; 95% CI, 1.85 - 11.42) were significantly associated with obesity. Screen time (OR, 4.68; 95% CI, 2.61-8.38; p=0.000) and having a computer in bedroom (OR, 1.7; 95% CI, 1.01- 2.87; p=0.046) were significantly associated with internet addiction, whereas parent’s compliant regarding the lengthy technology use (OR, 0.23; 95% CI, 0.11-0.46; p=0.000) was found to be a protective factor against internet addiction. Prolonged screen time, internet addiction, sedentary lifestyles, and reduced physical and social activities are interrelated, multi-dimensional factors that lead to obesity among children and adolescents. A family - school-based integrated approach should be implemented to tackle obesity problems.

Keywords: adolescents, internet addiction, lifestyle, Northern Cyprus, obesity, screen time

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Authors: Siti Nor Amira Bt. Mohamad, Mohamad Yazis B. Ali Basah, Muhammad Ridhwan B. Ab. Aziz, Khairil Faizal B. Khairi, Mazlynda Bt. Md. Yusuf, Hisham B. Sabri

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The understanding of risk and the concept of it occurs associated in Islamic financing was well-known in the financial industry by the using of Profit-and-Loss Sharing (PLS). It was presently in any Islamic financial transactions in order to comply with shariah rules. However, the existence of risk in Murabahah contract of financing is an ability that the counterparty is unable to complete its obligations within the agreed terms. Therefore, it is called as credit or default risk. Credit risk occurs when the client fails to make timely payment after the bank makes complete delivery of assets. Thus, it affects the growth of the bank as the banking business is in no position to have appropriate measures to cover the risk. Therefore, the bank may impose penalty on the outstanding balance. This paper aims to highlight the credit risk determinant and issues surrounding in Islamic bank in Malaysia in terms of Murabahah financing and how to manage it by using the proper techniques. Finally, it explores the credit risk management concept that might solve the problems arise. The study found that the credit risk can be managed properly by improving the use of comprehensive reference checklist of business partners on their character and past performance as well as their comprehensive database. Besides that, prevention of credit risk can be done by using collateral as security against the risk and we also argue on the Shariah guidelines and procedures should be implement coherently by the banking business because so that the risk would be control by having an effective instrument for Islamic modes of financing.

Keywords: Islamic banking, credit risk, Murabahah financing, risk mitigation

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Authors: Mariem Saadi, Sabri Kanzari, Adel Zghibi

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In semi-arid areas like the Kairouan region, the constant irrigation with saline water and the overuse of groundwater resources, soils and aquifers salinization has become an increasing concern. In this study, a methodology has been developed to evaluate the groundwater contamination risk based on the unsaturated zone hydraulic properties. Two soil profiles with different ranges of salinity, one located in the north of the plain and another one in the south of plain (each 30 m deep) and both characterized by direct recharge of the aquifer were chosen. Simulations were conducted with Hydrus-1D code using measured precipitation data for the period 1998-2003 and calculated evapotranspiration for both chosen profiles. Four combinations of initial conditions of water content and salt concentration were used for the simulation process in order to find the best match between simulated and measured values. The success of the calibration of Hydrus-1D allowed the investigation of some scenarios in order to assess the contamination risk under different natural conditions. The aquifer risk contamination is related to the natural conditions where it increased while facing climate change and temperature increase and decreased in the presence of a clay layer in the unsaturated zone. Hydrus-1D was a useful tool to predict the groundwater level and quality in the case of a direct recharge and in the absence of any information related to the soil layers except for the texture.

Keywords: Hydrus-1D, Kairouan, salinization, semi-arid region, solute transport, unsaturated zone

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Authors: Dairi Sabri, Mrad Dounia, Djebbar Yassine, Abida Habib

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Food security, which may be ensured by important agricultural production, needs huge amounts of water for irrigation. Recognizing this, the Algerian government made enormous efforts to mobilize water resources. Every drop of water collected, regardless of its origin, is needed to strengthen agricultural production. The present irrigated area in Algeria is about 1 million hectares while the potential agricultural area all over the country exceeds 9 million ha. This clearly shows the need for non-conventional water resources in Algeria, especially treated wastewater reuse. The use of treated wastewater in agricultural irrigation is still at the experimental stage in Algeria. While 20 million hectares worldwide are irrigated with treated wastewater, only 2300 hectares in Algeria are irrigated on an experimental basis in the regions of Setif, Constantine, Mila Telemcen, Tougourt and Boumerdès. The volume of wastewater discharged nationwide is estimated to be around 750 million cubic meters and is expected to exceed 1.5 billion m3 in 2020. An ambitious program of providing treatment facilities has been initiated in this direction to increase the treatment capacity to 2.5 million m3 per day in 2030. In order to optimize the use of this resource, specific research actions interested in defining treated wastewater reuse opportunities and standards are undertaken. The objective of this study is basically to examine the different components of treated wastewater reuse, including standards, treatment processes, agricultural opportunities and potentials as well as technical and economic aspects governing the feasibility of this technology in Algeria based on Geographic Information System (GIS).

Keywords: wastewater reuse, integrated management, irrigation, GIS

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Authors: Tarek Sabri Duzan

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Knowledge of the magnitude of Geo-pressures (Pore, Fracture & Over-burden pressures) is vital especially during drilling, completions, stimulations, Enhance Oil Recovery. Many times problems, like lost circulation could have been avoided if techniques for calculating Geo-pressures had been employed in the well planning, mud weight plan, and casing design. In this paper, we focused on the relationships between Geo-pressures and wave velocities (P-Wave (Vp) and S-wave (Vs)) in shallow Libyan carbonate reservoir in the western part of the Sirte Basin (Dahra F-Area). The data used in this report was collected from four new wells recently drilled. Those wells were scattered throughout the interested reservoir as shown in figure-1. The data used in this work are bulk density, Formation Mult -Tester (FMT) results and Acoustic wave velocities. Furthermore, Eaton Method is the most common equation used in the world, therefore this equation has been used to calculate Fracture pressure for all wells using dynamic Poisson ratio calculated by using acoustic wave velocities, FMT results for pore pressure, Overburden pressure estimated by using bulk density. Upon data analysis, it has been found that there is a linear relationship between Geo-pressures (Pore, Fracture & Over-Burden pressures) and wave velocities ratio (Vp/Vs). However, the relationship was not clear in the high-pressure area, as shown in figure-10. Therefore, it is recommended to use the output relationship utilizing the new seismic data for shallow carbonate reservoir to predict the Geo-pressures for future oil operations. More data can be collected from the high-pressure zone to investigate more about this area.

Keywords: bulk density, formation mult-tester (FMT) results, acoustic wave, carbonate shalow reservoir, d/jfield velocities

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Authors: Evrim Colak, Andriy E. Serebryannikov, Thore Magath, Ekmel Ozbay

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Single beam deflection and unidirectional transmission are examined for oblique incidence in a Photonic Crystal (PC) structure which employs defect layer instead of surface corrugations at the interfaces. In all of the studied cases, the defect layer is placed such that the symmetry is broken. Two types of deflection are observed depending on whether the zeroth order is coupled or not. These two scenarios can be distinguished from each other by considering the simulated field distribution in PC. In the first deflection type, Floquet-Bloch mode enables zeroth order coupling. The energy of the zeroth order is redistributed between the diffraction orders at the defect layer, providing deflection. In the second type, when zeroth order is not coupled, strong diffractions cause blazing and the evanescent waves deliver energy to higher order diffraction modes. Simulated isofrequency contours can be utilized to estimate the coupling behavior. The defect layer is placed at varying rows, preserving the asymmetry of PC while evancescent waves can still couple to higher order modes. Even for deeply buried defect layer, asymmetric transmission and beam deflection are still encountered when the zeroth order is not coupled. We assume ε=11.4 (refractive index close to that of GaAs and Si) for the PC rods. A possible operation wavelength can be within microwave and infrared range. Since the suggested material is low loss, the structure can be scaled down to operate higher frequencies. Thus, a sample operation wavelength is selected as 1.5μm. Although the structure employs no surface corrugations transmission value T≈0.97 can be achieved by means of diffraction order m=-1. Moreover, utilizing an extra line defect, T value can be increased upto 0.99, under oblique incidence even if the line defect layer is deeply embedded in the photonic crystal. The latter configuration can be used to obtain deflection in one frequency range and can also be utilized for the realization of another functionality like defect-mode wave guiding in another frequency range but still using the same structure.

Keywords: asymmetric transmission, beam deflection, blazing, bi-directional splitting, defect layer, dual beam splitting, Floquet-Bloch modes, isofrequency contours, line defect, oblique incidence, photonic crystal, unidirectionality

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Authors: Hadeer E. Eliwa, Naglaa S. Bazan, Ebtissam A. Darweesh, Nagwa A. Sabri

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Background: Generic substitution of brand ivabradine prescriptions can reduce drug expenditures and improve adherence. However, the distrust of generic medicines by practitioners and patients due to doubts regarding their quality and fear of counterfeiting compromise the acceptance of this practice. Aim: The goal of this study is to compare the therapeutic equivalence of brand product versus the generic product of ivabradine in adult patients with chronic heart failure with reduced ejection fraction (≤ 40%) (HFrEF). Methodology: Thirty-two Egyptian patients with chronic heart failure with reduced ejection fraction (HFrEF) were treated with branded ivabradine (Procrolan ©) and generic (Bradipect ©) during 24 (2x12) weeks. Primary outcomes were resting heart rate (HR), NYHA FC, Quality of life (QoL) using Minnesota Living with Heart Failure (MLWHF) and EF. Secondary outcomes were the number of hospitalizations for worsening HFrEF and adverse effects. The washout period was not allowed. Findings: At the 12th week, the reduction in HR was comparable in the two groups (90.13±7.11 to 69±11.41 vs 96.13±17.58 to 67.31±8.68 bpm in brand and generic groups, respectively). Also, the increase in EF was comparable in the two groups (27.44 ±4.59 to 33.38±5.62 vs 32±5.96 to 39.31±8.95 in brand and generic groups, respectively). The improvement in NYHA FC was comparable in both groups (87.5% in brand group vs 93.8% in the generic group). The mean value of the QOL improved from 31.63±15.8 to 19.6±14.7 vs 35.68±17.63 to 22.9±15.1 for the brand and generic groups, respectively. Similarly, at end of 24 weeks, no significant changes were observed from data observed at 12th week regarding HR, EF, QoL and NYHA FC. Only minor side effects, mainly phosphenes, and a comparable number of hospitalizations were observed in both groups. Conclusion: The study revealed no statistically significant differences in the therapeutic effect and safety between generic and branded ivabradine. We assume that practitioners can safely interchange between them for economic reasons.

Keywords: bradipect©, heart failure, ivabradine, Procrolan ©, therapeutic equivalence

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Authors: Sherif Sabri, Suzy Fawzi, Sanaa Abdelshafy, Ayman Nagah

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Introduction: Static derangements in lactate homeostasis during ICU stay have become established as a clinically useful marker of increased risk of hospital and ICU mortality. Lactate indices or kinetic alteration of the anaerobic metabolism make it a potential parameter to evaluate disease severity and intervention adequacy. This is an inexpensive and simple clinical parameter that can be obtained by a minimally invasive means. Aim of work: Comparing the predictive value of dynamic indices of hyperlactatemia in the first twenty four hours of intensive care unit (ICU) admission with other static values are more commonly used. Patients and Methods: This study included 40 critically ill patients above 18 years old of both sexes with Hyperlactamia (≥ 2 m mol/L). Patients were divided into septic group (n=20) and low oxygen transport group (n=20), which include all causes of low-O2. Six lactate indices specifically relating to the first 24 hours of ICU admission were considered, three static indices and three dynamic indices. Results: There were no statistically significant differences among the two groups regarding age, most of the laboratory results including ABG and the need for mechanical ventilation. Admission lactate was significantly higher in low-oxygen transport group than the septic group [37.5±11.4 versus 30.6±7.8 P-value 0.034]. Maximum lactate was significantly higher in low-oxygen transport group than the septic group P-value (0.044). On the other hand absolute lactate (mg) was higher in septic group P-value (< 0.001). Percentage change of lactate was higher in the septic group (47.8±11.3) than the low-oxygen transport group (26.1±12.6) with highly significant P-value (< 0.001). Lastly, time weighted lactate was higher in the low-oxygen transport group (1.72±0.81) than the septic group (1.05±0.8) with significant P-value (0.012). There were statistically significant differences regarding lactate indices in survivors and non survivors, whether in septic or low-oxygen transport group. Conclusion: In critically ill patients, time weighted lactate and percent in lactate change in the first 24 hours can be an independent predictive factor in ICU mortality. Also, a rising compared to a falling blood lactate concentration over the first 24 hours can be associated with significant increase in the risk of mortality.

Keywords: critically ill patients, lactate indices, mortality in intensive care, anaerobic metabolism

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Authors: Mohd Sabri Minhat, Nurul Adilla Mohd Subha

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The 1MWth PUSPATI TRIGA Reactor (RTP) in Malaysia Nuclear Agency has been operating more than 35 years. The existing core power control is using conventional controller known as Feedback Control Algorithm (FCA). It is technically challenging to keep the core power output always stable and operating within acceptable error bands for the safety demand of the RTP. Currently, the system could be considered unsatisfactory with power tracking performance, yet there is still significant room for improvement. Hence, a new design core power control is very important to improve the current performance in tracking and regulating reactor power by controlling the movement of control rods that suit the demand of highly sensitive of nuclear reactor power control. In this paper, the proposed Model Predictive Control (MPC) law was applied to control the core power. The model for core power control was based on mathematical models of the reactor core, MPC, and control rods selection algorithm. The mathematical models of the reactor core were based on point kinetics model, thermal hydraulic models, and reactivity models. The proposed MPC was presented in a transfer function model of the reactor core according to perturbations theory. The transfer function model-based predictive control (TFMPC) was developed to design the core power control with predictions based on a T-filter towards the real-time implementation of MPC on hardware. This paper introduces the sensitivity functions for TFMPC feedback loop to reduce the impact on the input actuation signal and demonstrates the behaviour of TFMPC in term of disturbance and noise rejections. The comparisons of both tracking and regulating performance between the conventional controller and TFMPC were made using MATLAB and analysed. In conclusion, the proposed TFMPC has satisfactory performance in tracking and regulating core power for controlling nuclear reactor with high reliability and safety.

Keywords: core power control, model predictive control, PUSPATI TRIGA reactor, TFMPC

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Authors: Yusuf Ersoy Yildirim, Ismail Tas, Ceren Gorgusen, Tugba Yeter, Aysegul Boyacioglu, K. Mehmet Tugrul, Murat Tugrul, Ayten Namli, H. Sabri Ozturk, M. Onur Akca

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In recent years, a lot of research has been done for the sustainable use of scarce resources in the world. Especially, effective and sustainable use of water resources has been researched for many years. Sub-surface drip irrigation (SDI) is one of the most effective irrigation methods in which efficient and sustainable use of irrigation water can be achieved. When the literature is taken into consideration, it is often emphasized that, besides its numerous advantages, it also allows the application of irrigation water to the plant root zone along with air. It is stated in different studies that the air applied to the plant root zone with irrigation water has a positive effect on the root zone. Plants need sufficient oxygen for root respiration as well as for the metabolic functions of the roots. Decreased root respiration due to low oxygen content reduces transpiration, disrupts the flow of ions, and increases the ingress of salt reaching toxic levels, seriously affecting plant growth. Lack of oxygen (Hypoxia) can affect the survival of plants. The lack of oxygen in the soil is related to the exchange of gases in the soil with the gases in the atmosphere. Soil aeration is an important physical parameter of a soil. It is highly dynamic and is closely related to the amount of water in the soil and its bulk weight. Subsurface drip irrigation; It has higher water use efficiency compared to irrigation methods such as furrow irrigation and sprinkler irrigation. However, in heavy clay soils, subsurface drip irrigation creates continuous wetting fronts that predispose the rhizosphere region to hypoxia or anoxia. With subsurface drip irrigation, the oxygen is limited for root microbial respiration and root development, with the continuous spreading of water to a certain region of the root zone. In this study, the change in sugar beet yield caused by air application in the SDI system will be explained.

Keywords: sugar beet, subsurface drip irrigation, air application, irrigation efficiency

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Authors: Tugbanur Ozen Balaban, Gultekin Tarcan, Unsal Gemici, Mumtaz Colak, I. Hakki Karamanderesi

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Buyuk Menderes Graben is located in the Western Anatolia (Turkey). The graben has become the largest industrial and agricultural area with a total population exceeding 3.000.000. There are two big cities within the study areas from west to east as Aydın and Denizli. The study area is very rich with regard to cold ground waters and thermal waters. Electrical production using geothermal potential has become very popular in the last decades in this area. Buyuk Menderes Graben is a tectonically active extensional region and is undergoing a north–south extensional tectonic regime which commenced at the latest during Early Middle Miocene period. The basement of the study area consists of Menderes massif rocks that are made up of high-to low-grade metamorphics and they are aquifer for both cold ground waters and thermal waters depending on the location. Neogene terrestrial sediments, which are mainly composed by alluvium fan deposits unconformably cover the basement rocks in different facies have very low permeability and locally may act as cap rocks for the geothermal systems. The youngest unit is Quaternary alluvium which is the shallow regional aquifer consists of Holocene alluvial deposits in the study area. All the waters are of meteoric origin and reflect shallow or deep circulation according to the 8O, 2H and 3H contents. Meteoric waters move to deep zones by fractured system and rise to the surface along the faults. Water samples (drilling well, spring and surface waters) and local seawater were collected between 2010 and 2012 years. Geochemical modeling was calculated distribution of the aqueous species and exchange processes by using PHREEQCi speciation code. Geochemical analyses show that cold ground water types are evolving from Ca–Mg–HCO3 to Na–Cl–SO4 and geothermal aquifer waters reflect the water types of Na-Cl-HCO3 in Aydın. Water types of Denizli are Ca-Mg-HCO3 and Ca-Mg-HCO3-SO4. Thermal water types reflect generally Na-HCO3-SO4. The B versus Cl rates increase from east to west with the proportion of seawater introduced into the fresh water aquifers and geothermal reservoirs. Concentrations of some elements (As, B, Fe and Ni) are higher than the tolerance limit of the drinking water standard of Turkey (TS 266) and international drinking water standards (WHO, FAO etc).

Keywords: Buyuk Menderes, isotope chemistry, geochemical modelling, water quality

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Authors: Evrim Colak, Andriy E. Serebryannikov, Pavel V. Usik, Ekmel Ozbay

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Working with a dielectric photonic crystal (PC) structure which does not include surface corrugations, unidirectional transmission and dual-beam splitting are observed under normal incidence as a result of the strong diffractions caused by the embedded defect layer. The defect layer has twice the period of the regular PC segments which sandwich the defect layer. Although the PC has even number of rows, the structural symmetry is broken due to the asymmetric placement of the defect layer with respect to the symmetry axis of the regular PC. The simulations verify that efficient splitting and occurrence of strong diffractions are related to the dispersion properties of the Floquet-Bloch modes of the photonic crystal. Unidirectional and bi-directional splitting, which are associated with asymmetric transmission, arise due to the dominant contribution of the first positive and first negative diffraction orders. The effect of the depth of the defect layer is examined by placing single defect layer in varying rows, preserving the asymmetry of PC. Even for deeply buried defect layer, asymmetric transmission is still valid even if the zeroth order is not coupled. This transmission is due to evanescent waves which reach to the deeply embedded defect layer and couple to higher order modes. In an additional selected performance, whichever surface is illuminated, i.e., in both upper and lower surface illumination cases, incident beam is split into two beams of equal intensity at the output surface where the intensity of the out-going beams are equal for both illumination cases. That is, although the structure is asymmetric, symmetric bidirectional transmission with equal transmission values is demonstrated and the structure mimics the behavior of symmetric structures. Finally, simulation studies including the examination of a coupled-cavity defect for two different permittivity values (close to the permittivity values of GaAs or Si and alumina) reveal unidirectional splitting for a wider band of operation in comparison to the bandwidth obtained in the case of a single embedded defect layer. Since the dielectric materials that are utilized are low-loss and weakly dispersive in a wide frequency range including microwave and optical frequencies, the studied structures should be scalable to the mentioned ranges.

Keywords: asymmetric transmission, beam deflection, blazing, bi-directional splitting, defect layer, dual beam splitting, Floquet-Bloch modes, isofrequency contours, line defect, oblique incidence, photonic crystal, unidirectionality

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Authors: Mohd Sabri Minhat, Nurul Adilla Mohd Subha

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The PUSPATI TRIGA Reactor (RTP), Malaysia reached its first criticality on June 28, 1982, with power capacity 1MW thermal. The Feedback Control Algorithm (FCA) which is conventional Proportional-Integral (PI) controller, was used for present power control method to control fission process in RTP. It is important to ensure the core power always stable and follows load tracking within acceptable steady-state error and minimum settling time to reach steady-state power. At this time, the system could be considered not well-posed with power tracking performance. However, there is still potential to improve current performance by developing next generation of a novel design nuclear core power control. In this paper, the dual-mode predictions which are proposed in modelling Optimal Model Predictive Control (OMPC), is presented in a state-space model to control the core power. The model for core power control was based on mathematical models of the reactor core, OMPC, and control rods selection algorithm. The mathematical models of the reactor core were based on neutronic models, thermal hydraulic models, and reactivity models. The dual-mode prediction in OMPC for transient and terminal modes was based on the implementation of a Linear Quadratic Regulator (LQR) in designing the core power control. The combination of dual-mode prediction and Lyapunov which deal with summations in cost function over an infinite horizon is intended to eliminate some of the fundamental weaknesses related to MPC. This paper shows the behaviour of OMPC to deal with tracking, regulation problem, disturbance rejection and caters for parameter uncertainty. The comparison of both tracking and regulating performance is analysed between the conventional controller and OMPC by numerical simulations. In conclusion, the proposed OMPC has shown significant performance in load tracking and regulating core power for nuclear reactor with guarantee stabilising in the closed-loop.

Keywords: core power control, dual-mode prediction, load tracking, optimal model predictive control

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Authors: Mahbuba Rahman, Sabri Boughorbel, Scott Presnell, Charlie Quinn, Darawan Rinchai, Damien Chaussabel, Nico Marr

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Collections of large-scale datasets made available in public repositories can be used to identify and fill gaps in biomedical knowledge. But first, these data need to be made readily accessible to researchers for analysis and interpretation. Here a collection of transcriptome datasets was made available to investigate the functional programming of human hematopoietic cells in early life. Thirty two datasets were retrieved from the NCBI Gene Expression Omnibus (GEO) and loaded in a custom, interactive web application called the Gene Expression browser (GXB), designed for visualization and query of integrated large-scale data. Multiple sample groupings and gene rank lists were created based on the study design and variables in each dataset. Web links to customized graphical views can be generated by users and subsequently be used to graphically present data in manuscripts for publication. The GXB tool also enables browsing of a single gene across datasets, which can provide information on the role of a given molecule across biological systems. The dataset collection is available online. As a proof-of-principle, one of the datasets (GSE25087) was re-analyzed to identify genes that are differentially expressed by regulatory T cells in early life. Re-analysis of this dataset and a cross-study comparison using multiple other datasets in the above mentioned collection revealed that PMCH, a gene encoding a precursor of melanin-concentrating hormone (MCH), a cyclic neuropeptide, is highly expressed in a variety of other hematopoietic cell types, including neonatal erythroid cells as well as plasmacytoid dendritic cells upon viral infection. Our findings suggest an as yet unrecognized role of MCH in immune regulation, thereby highlighting the unique potential of the curated dataset collection and systems biology approach to generate new hypotheses which can be tested in future mechanistic studies.

Keywords: early-life, GEO datasets, PMCH, interactive query, systems biology

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Authors: Abdulrazak Jinadu Otaru, Ahmed Almulhim, Hassan Alhassan, Mohammed Sabri

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Saudi Arabia is host to a state-owned oil and gas corporation, known as Saudi ARAMCO, that is responsible for the highest emissions of carbon dioxide (CO₂) due to the heavy reliance on fossil fuels as an energy source for various sectors such as transportation, aerospace, manufacturing, and residential use. Unfortunately, the detrimental consequences of CO₂ emissions include escalating temperatures in the Middle East region, posing significant obstacles in terms of food security and water scarcity for the Kingdom of Saudi Arabia. As part of the Saudi Vision 2030 initiative, which aims to reduce the country's reliance on fossil fuels by 50 %, this study focuses on designing a plant that will produce approximately 100,000 metric tons per year (MTPY) of green hydrogen (H₂) using brine as the primary feedstock. The proposed facility incorporates a double electrolytic technology that first separates brine or sodium chloride (NaCl) into sodium hydroxide, hydrogen gas, and chlorine gas. The sodium hydroxide is then used as an electrolyte in the splitting of water molecules through the supply of electrical energy in a second-stage electrolyser to produce green hydrogen. The study encompasses a comprehensive analysis of process descriptions and flow diagrams, as well as materials and energy balances. It also includes equipment design and specification, cost analysis, and considerations for safety and environmental impact. The design capitalizes on the abundant brine supply, a byproduct of the world's largest desalination plant located in Al Jubail, Saudi Arabia. Additionally, the design incorporates the use of available renewable energy sources, such as solar and wind power, to power the proposed plant. This approach not only helps reduce carbon emissions but also aligns with Saudi Arabia's energy transition policy. Furthermore, it supports the United Nations Sustainable Development Goals on Sustainable Cities and Communities (Goal 11) and Climate Action (Goal 13), benefiting not only Saudi Arabia but also other countries in the Middle East.

Keywords: plant design, electrolysis, brine, sodium hydroxide, chlorine gas, green hydrogen

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Authors: Sabri Sudirman, Yuan-Hua Hsu, Zwe-Ling Kong

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Male reproductive dysfunction is predominantly due to insulin resistance and hyperglycemia result in inflammation and oxidative stress. Furthermore, nanotechnology provides an alternative approach to improve the bioavailability of natural active food ingredients. Therefore, the aim of this study were to investigate nanoencapsulated triterpenoids from petri-dish cultured Antrodia cinnamomea (PAC) nanoparticles whether it could increase the bioavailability; in addition, the anti-inflammatory and anti-oxidative effects could more effectively ameliorate the reproductive function of diabetic male rats. First, PAC encapsulated in chitosan-silica nanoparticles (Nano-PAC) were prepared by biosilicification method. Scanning electron micrographs confirm the average particle size is about 30 nm, and the encapsulation efficiency is 83.7% by HPLC. Diabetic male Sprague-Dawley rats were induced by high fat diet (40% kcal from fat) and streptozotocin (35 mg/kg). Nano-PAC was administered by oral gavage in three doses (4, 8 and 20 mg/kg) for 6 weeks. Besides, metformin (300 mg/kg) and nanoparticles (Nano) were treated as the positive and negative control respectively. Results indicated that 4 mg/kg Nano-PAC administration for 6 weeks improved hyperglycemia, insulin resistance, and also reduced advanced glycation end products in plasma. In addition, 8 mg/kg Nano-PAC ameliorated morphological of testicular seminiferous tubules, sperm morphology and motility, reactive oxygen species production and mitochondrial membrane potential. Moreover, 20 mg/kg Nano-PAC restored reproductive endocrine system function and increased KiSS-1 level in plasma. In plasma or testis anti-oxidant superoxide dismutase, glutathione peroxidase and catalase were increased whereas malondialdehyde, as well as pro-inflammatory cytokines tumor necrosis factor-α, interleukin-6, and interferon-gamma, decreased. Most importantly, 8 mg/kg Nano-PAC down-regulated the oxidative stress induced c-Jun N-terminal kinase (JNK) signaling pathway. Our study successfully nanoencapsulated PAC to form nanoparticles and low-dose Nano-PAC improved diabetes-induced hyperglycemia, inflammation and oxidative stress to ameliorate the reproductive function of diabetic male rats.

Keywords: Antrodia cinnamomea, diabetes mellitus, male reproduction, nanoparticles

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Authors: Siti Noor Syahirah Mohd Sabri

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The oil and gas industry is committed to net zero carbon emissions because the consequences of climate change could be catastrophic unless responded to very soon. One way of reducing CO₂ emissions is to inject it into a depleted reservoir buried underground. This greenhouse gas reduction technique significantly reduces CO₂ released into the atmosphere. In general, depleted oil and gas reservoirs provide readily available sites for the storage of CO₂ in offshore areas. This is mainly due to the hydrocarbons have been optimally produced and the existence of voids for effective CO₂ storage. Hence, make it a good candidate for a CO₂ well injector location. Geological storage sites are often evaluated in terms of capacity, injectivity and containment. Leakage through the cap rock or existing well is the main concern in the depleted fields. In order to develop these fields as CO₂ storage sites, the long-term integrity of wells drilled in these oil & gas fields must be ascertained to ensure good CO₂ containment. Well, integrity is often defined as the ability to contain fluids without significant leakage through the project lifecycle. Most plugged and abandoned (P & A) wells in Peninsular Malaysia have drilled 20 – 30 years ago and were not designed to withstand downhole conditions having >50%vol CO₂ and CO₂/H₂O mixture. In addition, Corrosive-Resistant Alloy (CRA) tubular and CO₂-resistant cement was not used during good construction. The reservoir pressure and temperature conditions may have further degraded the material strength and elevated the corrosion rate. Understanding all the uncertainties that may have affected cement-casing bonds, such as the quality of cement behind the casing, subsidence effect, corrosion rate, etc., is the first step toward well integrity evaluation. Secondly, proper quantification of all the uncertainties involved needs to be done to ensure long-term underground storage objectives of CO₂ are achieved. This paper will discuss challenges associated with estimating the performance of well barrier elements in existing P&A wells. Risk ranking of the existing P&A wells is to be carried out in order to ensure the integrity of the storage site is maintained for long-term CO₂ storage. High-risk existing P&A wells are to be re-entered to restore good integrity and to reduce future leakage that may happen. In addition, the requirement to design a fit-for-purpose monitoring and mitigation technology package for potential CO₂ leakage/seepage in the marine environment will be discussed accordingly. The holistic approach will ensure that the integrity is maintained, and CO₂ is contained underground for years to come.

Keywords: CCUS, well integrity, co₂ storage, offshore

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Authors: Sabri Serkan Gulluoglu

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The study is aimed at examining the effects of internet marketing with IPTV on human beings. Internet marketing with IPTV is emerging as an integral part of business strategies in today’s technologically advanced world and the business activities all over the world are influences with the emergence of this modern marketing tool. As the population of the Internet and on-line users’ increases, new research issues have arisen concerning the demographics and psychographics of the on-line user and the opportunities for a product or service. In recent years, we have seen a tendency of various services converging to the ubiquitous Internet Protocol based networks. Besides traditional Internet applications such as web browsing, email, file transferring, and so forth, new applications have been developed to replace old communication networks. IPTV is one of the solutions. In the future, we expect a single network, the IP network, to provide services that have been carried by different networks today. For finding some important effects of a video based technology market web site on internet, we determine to apply a questionnaire on university students. Recently some researches shows that in Turkey the age of people 20 to 24 use internet when they buy some electronic devices such as cell phones, computers, etc. In questionnaire there are ten categorized questions to evaluate the effects of IPTV when shopping. There were selected 30 students who are filling the question form after watching an IPTV channel video for 10 minutes. This sample IPTV channel is “buy.com”, it look like an e-commerce site with an integrated IPTV channel on. The questionnaire for the survey is constructed by using the Likert scale that is a bipolar scaling method used to measure either positive or negative response to a statement (Likert, R) it is a common system that is used is the surveys. By following the Likert Scale “the respondents are asked to indicate their degree of agreement with the statement or any kind of subjective or objective evaluation of the statement. Traditionally a five-point scale is used under this methodology”. For this study also the five point scale system is used and the respondents were asked to express their opinions about the given statement by picking the answer from the given 5 options: “Strongly disagree, Disagree, Neither agree Nor disagree, Agree and Strongly agree”. These points were also rates from 1-5 (Strongly disagree, Disagree, Neither disagree Nor agree, Agree, Strongly agree). On the basis of the data gathered from the questionnaire some results are drawn in order to get the figures and graphical representation of the study results that can demonstrate the outcomes of the research clearly.

Keywords: IPTV, internet marketing, online, e-commerce, video based technology

Procedia PDF Downloads 240

Authors: F. Nur Baran Aksakal, Özge Dinç, H. Tanju Besler, Begüm Mutuş, Özlem Üliç Çatar, Orhan Aydoğdu, Serhat Ünal

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Healthy eating habits are associated not only with the newborn, child, and maternal health but also with longer life expectancy by acting as a protective factor against non-communicable diseases such as obesity, diabetes, cardiovascular diseases, and cancer. The role of nutrition in medical education is to provide information about the relationship between healthy nutrition and malnutrition as well as diet-related non-communicable diseases. Considering the information pollution experienced in the field of nutrition and health in the society, it is seen that more than half of the population receives information from family physicians as the closest counseling unit. However, postgraduate nutrition education programs for physicians and other health professionals who wish to improve their current knowledge of the role of nutrition communication in the prevention and management of chronic diseases are limited worldwide. However, nutrition courses are either not included in the undergraduate medical education curriculum of physicians or they are insufficient. Based on this need, the main aim of the study group was to develop a "Nutrition and Nutrition Communication Training for Physicians" program that would be conducted in cooperation with the Sabri Ülker Foundation and the Federation of Family Physicians Associations (AHEF). This program is the first online nutrition and nutrition communication information platform for physicians in Turkey. This program aims to present the concept of adequate and balanced nutrition to physicians, the importance of nutrition in diseases with scientific data, and to gain communication skills that may be necessary while transferring scientific information to the public. A needs assessment questionnaire was applied to identify pre-program training needs. A study plan was made to allow the participation of all family physicians in the population, and a complete inventory was targeted. In other words, we aimed to reach the whole source without taking a section of the population. Participation in the training is based on volunteerism. The needs assessment study is conducted using 25,102 family physicians for whom email addresses are available. The online questionnaire was sent to all the family physicians with a reminder email one week after the first one, and 1308 responded. Considering the topics determined, a training program was prepared for family physicians under eight online training titles, starting in March 2022, and conducted once every two weeks. The number of audience members present at each session was between 1217 and 1673, and a minimum of 17 and a maximum of 53 questions were received in each session. We strongly believe that to prevent individuals' health problems and to have better control over chronic diseases, the information level of physicians should be increased via these kinds of interventions, and better collaboration between family physicians and dieticians should be established.

Keywords: nutrition communication, nutrition training, communication, nutrition

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Authors: Minghui Zhang, Sirine Fkaier, Sabri Fernana, Svetlana Kiseleva, Denis Kiselev

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The real-time identification of bacteria and fungi is difficult because they emit much weaker signals than pollen. In 2020, Plair developed Rapid-E+, which extends abilities of Rapid-E to detect smaller bioaerosols such as bacteria and fungal spores with diameters down to 0.3 µm, while keeping the similar or even better capability for measurements of large bioaerosols like pollen. Rapid-E+ enables simultaneous measurements of (1) time-resolved, polarization and angle dependent Mie scattering patterns, (2) fluorescence spectra resolved in 16 channels, and (3) fluorescence lifetime of individual particles. Moreover, (4) it provides 2D Mie scattering images which give the full information on particle morphology. The parameters of every single bioaerosol aspired into the instrument are subsequently analysed by machine learning. Firstly, pure species of microbes, e.g., Bacillus subtilis (a species of bacteria), and Penicillium chrysogenum (a species of fungal spores), were aerosolized in a bioaerosol chamber for Rapid-E+ training. Afterwards, we tested microbes under different concentrations. We used several steps of data analysis to classify and identify microbes. All single particles were analysed by the parameters of light scattering and fluorescence in the following steps. (1) They were treated with a smart filter block to get rid of non-microbes. (2) By classification algorithm, we verified the filtered particles were microbes based on the calibration data. (3) The probability threshold (defined by the user) step provides the probability of being microbes ranging from 0 to 100%. We demonstrate how Rapid-E+ identified simultaneously microbes based on the results of Bacillus subtilis (bacteria) and Penicillium chrysogenum (fungal spores). By using machine learning, Rapid-E+ achieved identification precision of 99% against the background. The further classification suggests the precision of 87% and 89% for Bacillus subtilis and Penicillium chrysogenum, respectively. The developed algorithm was subsequently used to evaluate the performance of microbe classification and quantification in real-time. The bacteria and fungi were aerosolized again in the chamber with different concentrations. Rapid-E+ can classify different types of microbes and then quantify them in real-time. Rapid-E+ enables classifying different types of microbes and quantifying them in real-time. Rapid-E+ can identify pollen down to species with similar or even better performance than the previous version (Rapid-E). Therefore, Rapid-E+ is an all-in-one instrument which classifies and quantifies not only pollen, but also bacteria and fungi. Based on the machine learning platform, the user can further develop proprietary algorithms for specific microbes (e.g., virus aerosols) and other aerosols (e.g., combustion-related particles that contain polycyclic aromatic hydrocarbons).

Keywords: bioaerosols, laser-induced fluorescence, Mie-scattering, microorganisms

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Authors: Claire Harrison, Raajit K. Rampal, Vikas Gupta, Srdan Verstovsek, Moshe Talpaz, Jean-Jacques Kiladjian, Ruben Mesa, Andrew Kuykendall, Alessandro Vannucchi, Francesca Palandri, Sebastian Grosicki, Timothy Devos, Eric Jourdan, Marielle J. Wondergem, Haifa Kathrin Al-Ali, Veronika Buxhofer-Ausch, Alberto Alvarez-Larrán, Sanjay Akhani, Rafael Muñoz-Carerras, Yury Sheykin, Gozde Colak, Morgan Harris, John Mascarenhas

Abstract:

Myelofibrosis (MF) is characterized by bone marrow fibrosis, anemia, splenomegaly and constitutional symptoms. Progressive bone marrow fibrosis results from aberrant megakaryopoeisis and expression of proinflammatory cytokines, both of which are heavily influenced by bromodomain and extraterminal domain (BET)-mediated gene regulation and lead to myeloproliferation and cytopenias. Pelabresib (CPI-0610) is an oral small-molecule investigational inhibitor of BET protein bromodomains currently being developed for the treatment of patients with MF. It is designed to downregulate BET target genes and modify nuclear factor kappa B (NF-κB) signaling. MANIFEST-2 was initiated based on data from Arm 3 of the ongoing Phase 2 MANIFEST study (NCT02158858), which is evaluating the combination of pelabresib and ruxolitinib in Janus kinase inhibitor (JAKi) treatment-naïve patients with MF. Primary endpoint analyses showed splenic and symptom responses in 68% and 56% of 84 enrolled patients, respectively. MANIFEST-2 (NCT04603495) is a global, Phase 3, randomized, double-blind, active-control study of pelabresib and ruxolitinib versus placebo and ruxolitinib in JAKi treatment-naïve patients with primary MF, post-polycythemia vera MF or post-essential thrombocythemia MF. The aim of this study is to evaluate the efficacy and safety of pelabresib in combination with ruxolitinib. Here we report updates from a recent protocol amendment. The MANIFEST-2 study schema is shown in Figure 1. Key eligibility criteria include a Dynamic International Prognostic Scoring System (DIPSS) score of Intermediate-1 or higher, platelet count ≥100 × 10^9/L, spleen volume ≥450 cc by computerized tomography or magnetic resonance imaging, ≥2 symptoms with an average score ≥3 or a Total Symptom Score (TSS) of ≥10 using the Myelofibrosis Symptom Assessment Form v4.0, peripheral blast count <5% and Eastern Cooperative Oncology Group performance status ≤2. Patient randomization will be stratified by DIPSS risk category (Intermediate-1 vs Intermediate-2 vs High), platelet count (>200 × 10^9/L vs 100–200 × 10^9/L) and spleen volume (≥1800 cm^3 vs <1800 cm^3). Double-blind treatment (pelabresib or matching placebo) will be administered once daily for 14 consecutive days, followed by a 7 day break, which is considered one cycle of treatment. Ruxolitinib will be administered twice daily for all 21 days of the cycle. The primary endpoint is SVR35 response (≥35% reduction in spleen volume from baseline) at Week 24, and the key secondary endpoint is TSS50 response (≥50% reduction in TSS from baseline) at Week 24. Other secondary endpoints include safety, pharmacokinetics, changes in bone marrow fibrosis, duration of SVR35 response, duration of TSS50 response, progression-free survival, overall survival, conversion from transfusion dependence to independence and rate of red blood cell transfusion for the first 24 weeks. Study recruitment is ongoing; 400 patients (200 per arm) from North America, Europe, Asia and Australia will be enrolled. The study opened for enrollment in November 2020. MANIFEST-2 was initiated based on data from the ongoing Phase 2 MANIFEST study with the aim of assessing the efficacy and safety of pelabresib and ruxolitinib in JAKi treatment-naïve patients with MF. MANIFEST-2 is currently open for enrollment.

Keywords: CPI-0610, JAKi treatment-naïve, MANIFEST-2, myelofibrosis, pelabresib

Procedia PDF Downloads 201