Search results for: sliding control
Commenced in January 2007
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Edition: International
Paper Count: 10957

Search results for: sliding control

3157 Susceptibility Assessment and Genetic Diversity of Iranian and CIMMYT Wheat Genotypes to Common Root Rot Disease Bipolaris sorokiniana

Authors: Mehdi Nasr Esfahani, Abdal-Rasool Gholamalian, Abdelfattah A. Dababat

Abstract:

Wheat, Triticum aestivum L. is one of the most important and strategic crops in the human diet. Several diseases threaten this particular crop. Common root rot disease of wheat by a fungal agent, Bipolaris sorokiniana is one of the important diseases, causing considerable losses worldwide. Resistant sources are the only feasible and effective method of control for managing diseases. In this study, the response of 33 domestic and exotic wheat genotypes, including cultivars and promising lines were screened to B. sorokiniana at greenhouse and field conditions, based on five scoring scale indexes of 0 to 100 severity percentage. The screening was continued on resistant wheat genotypes and repeated several times to confirm the greenhouse and field results. Statistical and cluster analysis of data was performed using SAS and SPSS software, respectively. The results showed that, the response of wheat genotypes to the disease in the greenhouse and field conditions was highly significant. The highest rate of common root rot disease infection, B. sorokiniana in the greenhouse and field, was of CVS. Karkheh and Beck Cross-Roshan with 60.83% and 59.16% disease severity respectively, and the lowest one were in cv. Alvand with 18.33%, followed by cv. Baharan with 19.16% disease severity, with a highly significant difference respectively. The remaining wheat genotypes were located in between these two highest and lowest infected groups to B. sorokiniana significantly. There was a high correlation coefficient between the related statistical groups and cluster analysis.

Keywords: wheat, rot, root, crown, fungus, genotype, resistance

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3156 Kinetic Study on Extracting Lignin from Black Liquor Using Deep Eutectic Solvents

Authors: Fatemeh Saadat Ghareh Bagh, Srimanta Ray, Jerald Lalman

Abstract:

Lignin, the largest inventory of organic carbon with a high caloric energy value is a major component in woody and non-woody biomass. In pulping mills, a large amount of the lignin is burned for energy. At the same time, the phenolic structure of lignin enables it to be converted to value-added compounds.This study has focused on extracting lignin from black liquor using deep eutectic solvents (DESs). Therefore, three choline chloride (ChCl)-DESs paired with lactic acid (LA) (1:11), oxalic acid.2H₂O (OX) (1:4), and malic acid (MA) (1:3) were synthesized at 90oC and atmospheric pressure. The kinetics of lignin recovery from black liquor using DES was investigated at three moderate temperatures (338, 353, and 368 K) at time intervals from 30 to 210 min. The extracted lignin (acid soluble lignin plus Klason lignin) was characterized by Fourier transform infrared spectroscopy (FTIR). The FTIR studies included comparing the extracted lignin with a model Kraft lignin. The extracted lignin was characterized spectrophotometrically to determine the acid soluble lignin (ASL) [TAPPI UM 250] fraction and Klason lignin was determined gravimetrically using TAPPI T 222 om02. The lignin extraction reaction using DESs was modeled by first-order reaction kinetics and the activation energy of the process was determined. The ChCl:LA-DES recovered lignin was 79.7±2.1% at 368K and a DES:BL ratio of 4:1 (v/v). The quantity of lignin extracted for the control solvent, [emim][OAc], was 77.5+2.2%. The activation energy measured for the LA-DES system was 22.7 KJ mol⁻¹, while the activation energy for the OX-DES and MA-DES systems were 7.16 KJ·mol⁻¹ and 8.66 KJ·mol⁻¹ when the total lignin recovery was 75.4 ±0.9% and 62.4 ±1.4, % respectively.

Keywords: black liquor, deep eutectic solvents, kinetics, lignin

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3155 Controlling Fear: Jordanian Women’s Perceptions of the Diagnosis and Surgical Treatment of Early Stage Breast Cancer

Authors: Rana F. Obeidat, Suzanne S. Dickerson, Gregory G. Homish, Nesreen M. Alqaissi, Robin M. Lally

Abstract:

Background: Despite the fact that breast cancer is the most prevalent cancer among Jordanian women, practically nothing is known about their perceptions of early stage breast cancer and surgical treatment. Objective: To gain understanding of the diagnosis and surgical treatment experience of Jordanian women diagnosed with early stage breast cancer. Methods: An interpretive phenomenological approach was used for this study. A purposive sample of 28 Jordanian women who were surgically treated for early stage breast cancer within 6 months of the interview was recruited. Data were collected using individual interviews and analyzed using Heideggerian hermeneutical methodology. Results: Fear had a profound effect on Jordanian women’s stories of diagnosis and surgical treatment of early stage breast cancer. Women’s experience with breast cancer and its treatment was shaped by their pre-existing fear of breast cancer, the disparity in the quality of care at various health care institutions, and sociodemographic factors (e.g., education, age). Conclusions: Early after the diagnosis, fear was very strong and women lost perspective of the fact that this disease was treatable and potentially curable. To control their fears, women unconditionally trusted God, the health care system, surgeons, family, friends, and/or neighbors, and often accepted treatment offered by their surgeons without questioning. Implications for practice: Jordanian healthcare providers have a responsibility to listen to their patients, explore meanings they ascribe to their illness, and provide women with proper education and support necessary to help them cope with their illness.

Keywords: breast cancer, early stage, Jordanian, experience, phenomenology

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3154 Quorum Quenching Activities of Bacteria Isolated from Red Sea Sediments

Authors: Zahid Rehman, TorOve Leiknes

Abstract:

Quorum sensing (QS) is the process by which bacteria communicate with each other through small signaling molecules, such as N-acylhomoserine lactones (AHLs). Also, certain bacteria have the ability to degrade AHL molecules by a process referred to as quorum quenching (QQ); therefore, QQ can be used to control bacterial infections and biofilm formation. In this study, we aimed to identify new species of bacteria with QQ activities. To achieve this, sediments from Red Sea were collected either in the close vicinity of Sea grass or from area with no vegetation. From these samples, we isolated 72 bacterial strains and tested their ability to degrade/inactivate AHL molecules. Chromobacterium violaceum based bioassay was used in initial screening of isolates for QQ activity. The QQ activity of the positive isolates was further confirmed and quantified by employing liquid chromatography and mass spectrometry. These analyses showed that isolated bacterial strain could degrade AHL molecules with different acyl chain length and modifications. Sequencing of 16S-rRNA genes of positive isolates revealed that they belong to three different genera. Specifically, two isolates belong to genus Erythrobacter, four to Labrenzia and one isolate belongs to Bacterioplanes. Time course experiment showed that isolate belonging to genus Erythrobacter could degrade AHLs faster than other isolates. Furthermore, these isolates were tested for their ability to inhibit formation of biofilm and degradation of 3OXO-C12 AHLs produced by P. aeruginosa PAO1. Our results showed that isolate VG12 is better at controlling biofilm formation. This aligns with the ability of VG12 to cause at least 10-fold reduction in the amount of different AHLs tested.

Keywords: quorum sensing, biofilm, quorum quenching, anti-biofouling

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3153 Systematic Discovery of Bacterial Toxins Against Plants Pathogens Fungi

Authors: Yaara Oppenheimer-Shaanan, Nimrod Nachmias, Marina Campos Rocha, Neta Schlezinger, Noam Dotan, Asaf Levy

Abstract:

Fusarium oxysporum, a fungus that attacks a broad range of plants and can cause infections in humans, operates across different kingdoms. This pathogen encounters varied conditions, such as temperature, pH, and nutrient availability, in plant and human hosts. The Fusarium oxysporum species complex, pervasive in soils globally, can affect numerous plants, including key crops like tomatoes and bananas. Controlling Fusarium infections can involve biocontrol agents that hinder the growth of harmful strains. Our research developed a computational method to identify toxin domains within a vast number of microbial genomes, leading to the discovery of nine distinct toxins capable of killing bacteria and fungi, including Fusarium. These toxins appear to function as enzymes, causing significant damage to cellular structures, membranes and DNA. We explored biological control using bacteria that produce polymorphic toxins, finding that certain bacteria, non-pathogenic to plants, offer a safe biological alternative for Fusarium management, as they did not harm macrophage cells or C. elegans. Additionally, we elucidated the 3D structures of two toxins with their protective immunity proteins, revealing their function as unique DNases. These potent toxins are likely instrumental in microbial competition within plant ecosystems and could serve as biocontrol agents to mitigate Fusarium wilt and related diseases.

Keywords: microbial toxins, antifungal, Fusarium oxysporum, bacterial-fungal intreactions

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3152 Pattern of Bacterial Isolates and Antimicrobial Resistance at Ayder Comprehensive Specialized Referral Hospital in Northern Ethiopia: A Retrospective Study

Authors: Solomon Gebremariam, Mulugeta Naizigi, Aregawi Haileselassie

Abstract:

Background: Knowledge of the pattern of bacterial isolates and their antimicrobial susceptibility is crucial for guiding empirical treatment and infection prevention and control measures. Objective: The aim of this study was to analyze the pattern of bacterial isolates and their susceptibility patterns from various specimens. Methods: Retrospectively, a total of 1067 microbiological culture results that were isolated, characterized, and identified by standard microbiological methods and whose antibiotic susceptibility was determined using CLSI guidelines between 2017 and 2019 were retrieved and analyzed. Data were entered and analyzed using the Stata release 10.1 statistical package. Result: The positivity rate of culture was 26.04% (419/1609). The most common bacteria isolated were S. aureus 23.8% (94), E. coli 15.1% (60), Klebsiella pneumonia 14.1% (56), Pseudomonas aeruginosa 8.5% (34), and CONS 7.3% (29). S. aureus and CONS showed a high (58.1% - 96.2%) rate of resistance to most antibiotics tested. They were less resistant to Vancomycin which is 18.6% (13/70) and 11.8% (2/17), respectively. Similarly, the resistance of E. coli, Klebsella pneumonia, and Pseudomonas aeruginosa was high (69.4% - 100%) to most antibiotics. They were less resistant to Ciprofloxacilin, which is 41.1% (23/56), 19.2% (10/52), and 16.1% (5/31), respectively. Conclusion: This study has shown that there is a high rate of antibiotic resistance among bacterial isolates in this hospital. A combination of Vancomycin and Ciprofloxacin should be considered in the choice of antibiotics for empirical treatment of suspected infections due to S. aureus, CONS, E. coli, Klebsiella pneumonia, Pseudomonas such as in infections within hospital setup.

Keywords: antimicrobial, resistance, bacteria, hospital

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3151 Developing a Culturally Acceptable End of Life Survey (the VOICES-ESRD/Thai Questionnaire) for Evaluation Health Services Provision of Older Persons with End-Stage Renal Disease (ESRD) in Thailand

Authors: W. Pungchompoo, A. Richardson, L. Brindle

Abstract:

Background: The developing of a culturally acceptable end of life survey (the VOICES-ESRD/Thai questionnaire) is an essential instrument for evaluation health services provision of older persons with ESRD in Thailand. The focus of the questionnaire was on symptoms, symptom control and the health care needs of older people with ESRD who are managed without dialysis. Objective: The objective of this study was to develop and adapt VOICES to make it suitable for use in a population survey in Thailand. Methods: The mixed methods exploratory sequential design was focussed on modifying an instrument. Data collection: A cognitive interviewing technique was implemented, using two cycles of data collection with a sample of 10 bereaved carers and a prototype of the Thai VOICES questionnaire. Qualitative study was used to modify the developing a culturally acceptable end of life survey (the VOICES-ESRD/Thai questionnaire). Data analysis: The data were analysed by using content analysis. Results: The revisions to the prototype questionnaire were made. The results were used to adapt the VOICES questionnaire for use in a population-based survey with older ESRD patients in Thailand. Conclusions: A culturally specific questionnaire was generated during this second phase and issues with questionnaire design were rectified.

Keywords: VOICES-ESRD/Thai questionnaire, cognitive interviewing, end of life survey, health services provision, older persons with ESRD

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3150 An Overview of Paclitaxel as an Anti-Cancer Agent in Avoiding Malignant Metastatic Cancer Therapy

Authors: Nasrin Hosseinzad, Ramin Ghasemi Shayan

Abstract:

Chemotherapy is the most common procedure in the treatment of advanced cancers but is justsoberlyoperativeand toxic. Nevertheless, the efficiency of chemotherapy is restrictedowing to multiple drug resistance(MDR). Lately, plentiful preclinical experiments have revealedthatPaclitaxel-Curcumin could be an ultimateapproach to converse MDR and synergistically increase their efficiency. The connotationsamongst B-cell-lymphoma2(BCL-2) and multi-drug-resistance-associated-P-glycoprotein(MDR1) consequence of patients forecast the efficiency of paclitaxel-built chemoradiotherapy. There are evidences of the efficacy of paclitaxel in the treatment of surface-transmission of bladder-cell-carcinoma by manipulating bio-adhesive microspheres accomplishedthroughout measured release of drug at urine epithelium. In Genetically-Modified method, muco-adhesive oily constructionoftricaprylin, Tween 80, and paclitaxel group showed slighter toxicity than control in therapeutic dose. Postoperative chemotherapy-Paclitaxel might be more advantageous for survival than adjuvant chemo-radio-therapy, and coulddiminish postoperative complications in cervical cancer patients underwent a radical hysterectomy.HA-Se-PTX(Hyaluronic acid, Selenium, Paclitaxel) nanoparticles could observablyconstrain the proliferation, transmission, and invasion of metastatic cells and apoptosis. Furthermore, they exhibitedvast in vivo anti-tumor effect. Additionally, HA-Se-PTX displayedminor toxicity on mice-chef-organs. Briefly, HA-Se-PTX mightprogress into a respectednano-scale agentinrespiratory cancers. To sum up, Paclitaxel is considered a profitable anti-cancer drug in the treatment and anti-progress symptoms in malignant cancers.

Keywords: cancer, paclitaxel, chemotherapy, tumor

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3149 Subjective Well-Being in Individuals Diagnosed with an Autoimmune Disease: Resilience, and Rumination as Moderating Factors

Authors: Renae McNair

Abstract:

Subjective well-being levels were assessed in individuals diagnosed with an autoimmune disease. The current exploratory analysis sought to examine two factors that impact subjective well-being in individuals diagnosed with a chronic health condition. The two factors, resilience, and rumination, were assessed as possible moderators in self-reported levels of subjective well-being were measured. The importance of understanding the psychological state of perceived well-being in an individual diagnosed with an autoimmune disease is important given the impact of the level of subjective well-being on life longevity. In previous research, higher levels of subjective well-being are correlated with longer life longevity, including those individuals who have been diagnosed with an autoimmune disease. Conversely, individuals who report higher levels of negative affect have a shorter length of life longevity. According to the Center for Disease Control (CDC) and a report from the National Health Council, currently, 8-10% of individuals in the United States have been diagnosed with at least one autoimmune disease. Although treatment plans are in place to help manage the physical effects of disease, the psychological state of the person impacts life longevity. Resilience and rumination impact subjective well-being as an outcome in individuals diagnosed with an autoimmune disease. Resilience is the ability to adjust or adapt effectively and positively to unfavorable life conditions or events. Resilience acts as a protective factor in life, allowing those who face adversity to successfully adapt, regardless of the health diagnosis. Rumination is the worry or dwelling on the negative aspects of a given situation. Rumination interrupts the adaptive response, leading to a decrease in well-being. The relationship between resilience and subjective well-being were examined correlated with higher levels of resilience and higher levels of self-reported subjective well-being.

Keywords: subjective well-being, rumination, resilience, autoimmune disease

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3148 Wheat (Triticum Aestivum) Yield Improved with Irrigation Scheduling under Salinity

Authors: Taramani Yadav, Gajender Kumar, R.K. Yadav, H.S. Jat

Abstract:

Soil Salinity and irrigation water salinity is critical threat to enhance agricultural food production to full fill the demand of billion plus people worldwide. Salt affected soils covers 6.73 Mha in India and ~1000 Mha area around the world. Irrigation scheduling of saline water is the way to ensure food security in salt affected areas. Research experiment was conducted at ICAR-Central Soil Salinity Research Institute, Experimental Farm, Nain, Haryana, India with 36 treatment combinations in double split plot design. Three sets of treatments consisted of (i) three regimes of irrigation viz., 60, 80 and 100% (I1, I2 and I3, respectively) of crop ETc (crop evapotranspiration at identified respective stages) in main plot; (ii) four levels of irrigation water salinity (sub plot treatments) viz., 2, 4, 8 and 12 dS m-1 (iii) applications of two PBRs along with control (without PBRs) i.e. salicylic acid (G1; 1 mM) and thiourea (G2; 500 ppm) as sub-sub plot treatments. Grain yield of wheat (Triticum aestivum) was increased with less amount of high salt loaded irrigation water at the same level of salinity (2 dS m-1), the trend was I3>I2>I1 at 2 dS m-1 with 8.10 and 17.07% increase at 80 and 100% ETc, respectively compared to 60% ETc. But contrary results were obtained by increasing amount of irrigation water at same level of highest salinity (12 dS m-1) showing following trend; I1>I2>I3 at 12 dS m-1 with 9.35 and 12.26% increase at 80 and 60% ETc compared to 100% ETc. Enhancement in grain yield of wheat (Triticum aestivum) is not need to increase amount of irrigation water under saline condition, with salty irrigation water less amount of irrigation water gave the maximum wheat (Triticum aestivum) grain yield.

Keywords: Irrigation, Salinity, Wheat, Yield

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3147 Endeavor in Management Process by Executive Dashboards: The Case of the Financial Directorship in Brazilian Navy

Authors: R. S. Quintal, J. L. Tesch Santos, M. D. Davis, E. C. de Santana, M. de F. Bandeira dos Santos

Abstract:

The objective is to identify the contributions from the introduction of the computerized system deal within the Accounting Department of Brazilian Navy Financial Directorship and its possible effects on the budgetary and financial harvest of Brazilian Navy. The relevance lies in the fact that the management process is responsible for the continuous improvement of organizational performance through higher levels of quality in their activities. Improvements in organizational processes have direct effects on crops cost, quality, reliability, flexibility and speed. The method of study of this research is the case study. The choice of case study attended, among other demands, a need for greater flexibility to study processes related to a computerized system. The sources of evidence were used literature, documentary and direct observation. Direct observation was made by monitoring the implementation of the computerized system in the Division of Management Analysis. The main findings of the study point to the fact that the computerized system may contribute significantly to the standardization of information. There was improvement of internal processes in the division of management analysis, made possible the consolidation of a standard management and performance analysis that contribute to global homogeneity in the treatment of information essential to the process of decision making. This study has limitations related to the fact the search result be subject exclusively to the case studied, and it is impossible to generalize to other organs of government.

Keywords: process management, management control, business intelligence, Brazilian Navy

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3146 A Randomized Controlled Intervention Study of the Effect of Music Training on Mathematical and Working Memory Performances

Authors: Ingo Roden, Stefana Lupu, Mara Krone, Jasmin Chantah, Gunter Kreutz, Stephan Bongard, Dietmar Grube

Abstract:

The present experimental study examined the effects of music and math training on mathematical skills and visuospatial working memory capacity in kindergarten children. For this purpose, N = 54 children (mean age: 5.46 years; SD = .29) were randomly assigned to three groups. Children in the music group (n = 18) received weekly sessions of 60 min music training over a period of eight weeks, whereas children in the math group (n = 18) received the same amount of training focusing on mathematical basic skills, such as numeracy skills, quantity comparison, and counting objectives. The third group of children (n = 18) served as waiting controls. The groups were matched for sex, age, IQ and previous music experiences at baseline. Pre-Post intervention measurements revealed a significant interaction effect of group x time, showing that children in both music and math groups significantly improved their early numeracy skills, whereas children in the control group did not. No significant differences between groups were observed for the visuospatial working memory performances. These results confirm and extend previous findings on transfer effects of music training on mathematical abilities and visuospatial working memory capacity. They show that music and math interventions are similarly effective to enhance children’s mathematical skills. More research is necessary to establish, whether cognitive transfer effects arising from music interventions might facilitate children’s transition from kindergarten to first-grade.

Keywords: music training, mathematical skills, working memory, transfer

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3145 Genetics of Atopic Dermatitis: Role of Cytokine Genes Polymorphisms

Authors: Ghaleb Bin Huraib

Abstract:

Atopic dermatitis (AD), also known as atopic eczema, is a chronic inflammatory skin disease characterized by severe itching and recurrent, relapsing eczema-like skin lesions, affecting up to 20% of children and 10% of adults in industrialized countries. AD is a complex multifactorial disease, and its exact etiology and pathogenesis have not been fully elucidated. The aim of this study was to investigate the impact of gene polymorphisms of T helper cell subtype Th1 and Th2 cytokines, interferon-gamma (IFN-γ), interleukin-6 (IL-6) and transforming growth factor (TGF)-β1on AD susceptibility in a Saudi cohort. One hundred four unrelated patients with AD and 195 healthy controls were genotyped for IFN-γ (874A/T), IL-6 (174G/C) and TGF-β1 (509C/T) polymorphisms using ARMS-PCR and PCR-RFLP technique. The frequency of genotypes AA and AT of IFN-γ (874A/T) differed significantly among patients and controls (P 0.001). The genotype AT was increased while genotype AA was decreased in AD patients as compared to controls. AD patients also had a higher frequency of T-containing genotypes (AT+TT) than controls (P = 0.001). The frequencies of alleles T and A were statistically different in patients and controls (P = 0.04). The frequencies of genotype GG and allele G of IL-6 (174G/C) were significantly higher, while genotype GC and allele C were lower in AD patients than in controls. There was no significant difference in the frequencies of alleles and genotypes of TGF-β1 (509C/T) polymorphism between the patient and control groups. These results showed that susceptibility to AD is influenced by the presence or absence of genotypes of IFN-γ (874A/T) and IL-6 (174G/C) polymorphisms. It is concluded T-allele and T-containing genotypes (AT+TT) of IFN-γ (874A/T) and G-allele and GG genotype ofIL-6 (174G/C) polymorphisms are susceptible to AD in Saudis. On the other hand, the TGF-β1 (509C/T) polymorphism may not be associated with AD risk in our population; however, further studies with large sample sizes are required to confirm these results.

Keywords: atopic dermatitis, Polymorphism, Interferon, IL-6

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3144 Law, Regulatory Transformations and Evolving Paradigm: The Case of Corporate Social Responsibility in India

Authors: Shuchi Bharti

Abstract:

This article intends to analyse the transforming nature of state and corporate sector relationship in the light of evolving regulatory and institutional aspects pertaining to Corporate Social Responsibility (CSR) in India. The focus is on evaluating the accounts of law and decentred discourses, relevant within the changing regulatory and institutional paradigm that substantially goes ahead of formal legal control of state towards corporate actors. At this vantage point, it is important to understand the state’s posture towards a changing scenario particularly as the tone is set by regulatory parameters pertaining to CSR to drive process of engagement with the stakeholders. The tripartite framework of the article intends to focus on finding on the vital interconnected aspects of the CSR provisions (Section 135) of The Companies Act 2013 (The Act), rise of new institutions and the emergence of the decentred regulatory space. Thus is earmarked in a neo-liberal paradigm; state is witnessed to perform a responsive function in engendering enhanced public role for the corporate sector. In this overarching framework the aim is to undertake a causal, exploratory and relational analysis of aspects pertaining law, regulation and institutional transformations. Firstly, focus is drawn on to investigate the relational facets of the advent of law and regulatory framework of CSR. Secondly, in the light of the historical evolution, a causal connection is attempted between globalization, emergence of international soft law framework and the Indian case of CSR. Finally, I look into how the new Companies Act mandates CSR expenditure vis- a -vis multiple parameters and guidelines.

Keywords: corporate social responsibility, stakeholders, soft law, decentred regulation

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3143 Effect of Relaxation Techniques on Immunological Properties of Breast Milk

Authors: Ahmed Ali Torad

Abstract:

Background: Breast feeding maintains the maternal fetal immunological link, favours the transmission of immune-competence from the mother to her infant and is considered an important contributory factor to the neo natal immune defense system. Purpose: This study was conducted to investigate the effect of relaxation techniques on immunological properties of breast milk. Subjects and Methods: Thirty breast feeding mothers with a single, mature infant without any complications participated in the study. Subjects will be recruited from outpatient clinic of obstetric department of El Kasr El-Aini university hospital in Cairo. Mothers were randomly divided into two equal groups using coin toss method: Group (A) (relaxation training group) (experimental group): It will be composed of 15 women who received relaxation training program in addition to breast feeding and nutritional advices and Group (B) (control group): It will be composed of 15 women who received breast feeding and nutritional advices only. Results: The results showed that mean mother’s age was 28.4 ± 3.68 and 28.07 ± 4.09 for group A and B respectively, there were statistically significant differences between pre and post values regarding cortisol level, IgA level, leucocyte count and infant’s weight and height and there is only statistically significant differences between both groups regarding post values of all immunological variables (cortisol – IgA – leucocyte count). Conclusion: We could conclude that there is a statistically significant effect of relaxation techniques on immunological properties of breast milk.

Keywords: relaxation, breast, milk, immunology, lactation

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3142 Association of Human Immunodeficiency Virus with Incident Autoimmune Hemolytic Anemia: A Population-Based Cohort Study in Taiwan

Authors: Yung-Feng Yen, I-an Jen, Yi-Ming Arthur Chen

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The molecular mimicry between human immunodeficiency virus (HIV) protein and red blood cell (RBC) antigens could induce the production of anti-RBC autoantibodies. However, the association between HIV infection and subsequent development of autoimmune hemolytic anemia (AIHA) remains unclear. This nationwide population-based cohort study aimed to determine the association between incident AIHA and HIV in Taiwan. From 2000–2012, we identified adult people living with HIV/AIDS (PLWHA) from the Taiwan centers for disease control HIV Surveillance System. HIV-infected individuals were defined by positive HIV-1 western blot. Age- and sex-matched controls without HIV infection were selected from the Taiwan National Health Insurance Research Database for comparison. All patients were followed until Dec. 31, 2012, and observed for occurrence of AIHA. Of 171,468 subjects (19,052 PLWHA, 152,416 controls), 30 (0.02%) had incident AIHA during a mean follow-up of 5.45 years, including 23 (0.12%) PLWHA and 7 (0.01%) controls. After adjusting for potential confounders, HIV infection was found to be an independent risk factor of incident AIHA (adjusted hazard ratio [AHR], 20.9; 95% confidence interval [CI], 8.34-52.3). Moreover, PLWHA receiving HAART were more likely to develop AIHA than those not receiving HAART (AHR, 10.8; 95% CI, 2.90-40.1). Additionally, the risk of AIHA was significantly increased in those taking efavirenz (AHR, 3.15; 95% CI, 1.18-8.43) or atazanavir (AHR, 6.58; 95% CI, 1.88-22.9) component of the HAART. In conclusion, HIV infection is an independent risk factor for incident AIHA. Clinicians need to be aware of the higher risk of AIHA in PLWHA.

Keywords: autoimmune disease , hemolytic anemia, HIV, highly active antiretroviral treatment

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3141 In vivo Inhibition and Restoration of Acetyl Cholinesterase Activities in Induced Clarias Gariepinus

Authors: T. O. Ikpesu, I. Tongo, A. Ariyo

Abstract:

This study was conducted to assess the effects of an organophosphate pesticide glyphosate formulation on neurological enzymes in the brain, liver and serum of juvenile Clarias gariepinus, and also to examine the antidotal prospect of Garcinia kola seeds extract. The fish divided into five groups were exposed to different treatments of glyphosate formulation and Garcinia kola seeds extract. Acetyl cholinesterase activities in the brain, liver and serum of the fish were estimated in the experimental and control fishes on day -7, 14, 21 and of 28 by spectrophotometrical methods. The enzyme was significantly (p < 0.05) inhibited in glyphosate formulation test. The inhibition percentages of AChE ranged for the brain, liver and serum between 40.7–59.4%, 50-57% and 27.5–51.3%, respectively. The aberrated parameters were recovered in G. kola seeds extract treated aquaria, and was dose and time dependent. The present study demonstrated that in vivo glyphosate formulation exposure caused AChE inhibition in the brain, liver and the serum. The brain tissue, however, might be suggested as a good indicator tissue for aquatic pollutants exposure in the fish and G. kola seeds extract has shown to be a good remedy for neurology restoration in a noxious circumstance. The findings has shown that xenobiotics could be eliminated from aquatic organisms, especially fish, and could be put into practice in areas at risk of pollutants. This approach can reduce the risks of biomagnification of poison in sea food. Hence, formulation of this plant extracts into capsule should be encouraged and supported.

Keywords: glyphosate, Clarias gariepinus, brain, Garcinia kola, acetyl cholinesterase, enzymes

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3140 Generalized Linear Modeling of HCV Infection Among Medical Waste Handlers in Sidama Region, Ethiopia

Authors: Birhanu Betela Warssamo

Abstract:

Background: There is limited evidence on the prevalence and risk factors for hepatitis C virus (HCV) infection among waste handlers in the Sidama region, Ethiopia; however, this knowledge is necessary for the effective prevention of HCV infection in the region. Methods: A cross-sectional study was conducted among randomly selected waste collectors from October 2021 to 30 July 2022 in different public hospitals in the Sidama region of Ethiopia. Serum samples were collected from participants and screened for anti-HCV using a rapid immunochromatography assay. Socio-demographic and risk factor information of waste handlers was gathered by pretested and well-structured questionnaires. The generalized linear model (GLM) was conducted using R software, and P-value < 0.05 was declared statistically significant. Results: From a total of 282 participating waste handlers, 16 (5.7%) (95% CI, 4.2 – 8.7) were infected with the hepatitis C virus. The educational status of waste handlers was the significant demographic variable that was associated with the hepatitis C virus (AOR = 0.055; 95% CI = 0.012 – 0.248; P = 0.000). More married waste handlers, 12 (75%), were HCV positive than unmarried, 4 (25%) and married waste handlers were 2.051 times (OR = 2.051, 95%CI = 0.644 –6.527, P = 0.295) more prone to HCV infection, compared to unmarried, which was statistically insignificant. The GLM showed that exposure to blood (OR = 8.26; 95% CI = 1.878–10.925; P = 0.037), multiple sexual partners (AOR = 3.63; 95% CI = 2.751–5.808; P = 0.001), sharp injury (AOR = 2.77; 95% CI = 2.327–3.173; P = 0.036), not using PPE (AOR = 0.77; 95% CI = 0.032–0.937; P = 0.001), contact with jaundiced patient (AOR = 3.65; 95% CI = 1.093–4.368; P = 0 .0048) and unprotected sex (AOR = 11.91; 95% CI = 5.847–16.854; P = 0.001) remained statistically significantly associated with HCV positivity. Conclusions: The study revealed that there was a high prevalence of hepatitis C virus infection among waste handlers in the Sidama region, Ethiopia. This demonstrated that there is an urgent need to increase preventative efforts and strategic policy orientations to control the spread of the hepatitis C virus.

Keywords: Hepatitis C virus, risk factors, waste handlers, prevalence, Sidama Ethiopia

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3139 The Impact of Diabetes Mellitus on Skin and Soft Tissue Infections

Authors: Stephanie Cheng, Benjamin Poh, Vivyan Tay, Sachin Mathur

Abstract:

Aim: Diabetes mellitus (DM) is a worldwide pandemic affecting 500 million people. It is known to be associated with increased susceptibility to soft tissue infections (STI). Despite being a major public health burden, the literature relating the effects of DM and the presentation, severity and healing of STIs in general surgical patients remain limited. Methods: We conducted a retrospective review of all patients admitted with STI in a tertiary teaching hospital over a 12-month period. Patient demographics and surgical outcomes were collected and analyzed. Results: During the study period, 1059 patients were admitted for STIs, of which 936 (88%) required surgical intervention. Diabetic patients were presented with a higher body-mass index (BMI) (28 vs 26), larger abscess size (24 vs 14 cm²) and a longer length of stay (LOS)(4.4 days vs 2.9 days). They also underwent a higher proportion of wide debridement as well as application of negative pressure wound therapy (NPWT) (42% vs 35%). More diabetic patients underwent subsequent re-operation within the same sitting (8 vs 4). There were no differences in re-admission rates within 30 days nor subsequent abscess formation in those followed for 6 months. Conclusion: The incidence of STIs among DM patients represents a significant disease burden; surgeons should consider intensive patient counseling and partnering with primary care providers in order to help reduce the incidence of future STI admissions based on lifestyle modification and glucose control.

Keywords: general surgery, emergency general surgery, acute care surgery, soft tissue infections, diabetes mellitus

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3138 In silico Analysis of a Causative Mutation in Cadherin-23 Gene Identified in an Omani Family with Hearing Loss

Authors: Mohammed N. Al Kindi, Mazin Al Khabouri, Khalsa Al Lamki, Tommasso Pappuci, Giovani Romeo, Nadia Al Wardy

Abstract:

Hereditary hearing loss is a heterogeneous group of complex disorders with an overall incidence of one in every five hundred newborns presented as syndromic and non-syndromic forms. Cadherin-related 23 (CDH23) is one of the listed deafness causative genes. CDH23 is found to be expressed in the stereocilia of hair cells and the retina photoreceptor cells. Defective CDH23 has been associated mostly with prelingual severe-to-profound sensorineural hearing loss (SNHL) in either syndromic (USH1D) or non-syndromic SNHL (DFNB12). An Omani family diagnosed clinically with severe-profound sensorineural hearing loss was genetically analysed by whole exome sequencing technique. A novel homozygous missense variant, c.A7451C (p.D2484A), in exon 53 of CDH23 was detected. One hundred and thirty control samples were analysed where all were negative for the detected variant. The variant was analysed in silico for pathogenicity verification using several mutation prediction software. The variant proved to be a pathogenic mutation and is reported for the first time in Oman and worldwide. It is concluded that in silico mutation prediction analysis might be used as a useful molecular diagnostics tool benefiting both genetic counseling and mutation verification. The aspartic acid 2484 alanine missense substitution might be the main disease-causing mutation that damages CDH23 function and could be used as a genetic hearing loss marker for this particular Omani family.

Keywords: Cdh23, d2484a, in silico, Oman

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3137 Study on the Effect Cabbage (Brassica oleracea) and Ginger (Zingiber officinale) Extracts on Rat Liver Injuries Induced by Carbon tetrachloride (CCl4)

Authors: Asmaa F. Hamouda, Randa M Shrourou

Abstract:

Cabbage (Brassica oleracea) and Ginger (Zingiber officinale) constitute apportion of regular human diet. The effect of Cabbage(CE) and Ginger extracts(GE) separately on liver nitric oxide (NO), malondialdehyde (MDA), as well as serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, total cholesterol(TC), triglyceride(T.G), high density lipoprotein(HDL cholesterol), low density lipoprotein (LDL cholesterol), thyroid-stimulating hormone (TSH), Triiodothyronine (T3), Thyroxine (T4) in rats treated and untreated with carbon tetrachloride (CCl4) was studied. The levels of NO, MDA, as well as serum AST, ALT, total bilirubin, TC, T.G, LDLand TSH showed an elevation and decline in HDL, T3, and T4 in rats treated with CCl4 as compared to control. Treatment of rats with GE pre, during, and post CCl4 administration improved NO, MDA, as well as serum AST, ALT, total bilirubin, TC, T.G, HDL, LDL, TSH, T3, T4 as compared to CCl4, indicates that GE improve thyroid function and reduced oxidative stress as well as injuries induced by CCl4. Treatment of rats with CE pre, during, and post CCl4 administration did not improved in the thyroid hormones and lipid profile levels as compared to CCl4. These findings suggest that ginger treatment exerts a protective effect on metabolic disorders by decreasing oxidative stress.

Keywords: liver injuries, carbon tetrachloride (CCl4), cabbage (Brassica oleracea), ginger (Zingiber officinale), thyroid function

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3136 Impact of Edible Coatings Made of Chitosan and Spray Dried Propolis in the Shell Life of White Cachama (Piaractus brachypomus)

Authors: David Guillermo Piedrahita Marquez, Hector Suarez Mahecha, Jairo Humberto Lopez

Abstract:

There is a need to preserve aquaculture matrices due to their high nutritional value, and its broad consumption, one of those species is the white cachama (Piaractus brachypomus), this fish is located in the rivers of eastern Colombia, and the previously mentioned species needs more study. Therefore, in a paper the effects of an alternative method of preservation of shell life were investigated, the method used is the application of an edible coating made from chitosan and ethanolic extract of propolis (EEP) encapsulated in maltodextrin. The coating was applied by immersion, and after that, we investigated the post mortem quality changes of the fish performing physicochemical and microbiological analysis. pH, volatile bases, test thiobarbituric acid and peroxide value were tested; finally, we studied the effect of the coating on mesophilic strains, coliforms and other microorganisms such as Staphylococcus, and Salmonella. Finally, we concluded that the coating prolongs the shelf life because it acts as a barrier to oxygen and moisture, the bioactive compounds trap free radicals and the coatings changes the metabolism and cause the cell lysis of the microorganisms. It was determined that the concentration of malonaldehyde, the volatile basic nitrogen content and pH are the variables that distinguish more clearly between the samples with the treatment and the control samples.

Keywords: antimicrobial activity, lipid oxidation, texture profile analysis (TPA), sensorial analysis, peroxide value, thiobarbituric acid assay (TBA), total volatile basic nitrogen (TVB-N)

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3135 Animal Welfare Violations during Treatment at Different Level of Veterinary Hospitals

Authors: Aparna Datta, Mahabub Alam

Abstract:

Animal welfare is comparatively new area of research in Bangladesh and welfare concern for animal is increasing day by day. The study was conducted to investigate the animal welfare violations during treatment at different level of hospitals in Bangladesh and India. This study was conducted between January and May, 2017. The recorded data (N=180) were categorized into eight major types of violation like - delay in starting treatment, non-specific treatment, surgery without anesthesia, use of unsterilized needle, rough and painful handling, fearful approach, multiple pricking during injection and use of blunt needle. Categorized groups were analyzed according to different hospitals like Upazila Veterinary Hospitals, Bangladesh (UVHs), SAQ-Teaching Veterinary Hospital, Bangladesh (SAQTVH) and Veterinary College and Research Institute, India (VCRI). Among all hospitals, violation during treatment more frequently occurred in UVH. Among all violations, surgery without anesthesia was only found in UVH (80%) and it was belong to considerable number of cases (80%). In the view of other major violations like - non-specific treatment was 69% in UVHs, 13% in SAQTVH and 5% in VCRI. Use of unsterilized instruments during treatment was also higher in UVHs (65%) than SAQTVH (5%) and VCRI (1%). But delay in starting treatment varied insignificantly and it was 26-42% across the different levels of hospitals. Although multiple pricking during injection was found 30% cases in UVH, but statistical variations with other level of hospitals were unnoticed (p>0.05). The findings of this study will help to take necessary steps to control violation against animal welfare during treatment. A comprehensive study considering all levels of hospitals including field treatment is also recommended to find out the welfare violations during treatment.

Keywords: animal welfare, treatment, veterinary hospitals, violations

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3134 Examining the Factors That Mediate the Effects of Mindfulness on Conflict Resolution Strategies

Authors: Franco Ceasar Agbalog, Shintaro Yukawa

Abstract:

Mindfulness is increasingly being used as a method for resolving conflict. However, less is known about how its positive outcome develops. To better understand the underlying effects of mindfulness on conflict resolution strategies, this study examines the potential mediating factors between them. The researchers hypothesized that Emotional Intelligence (EI) mediates the effects of mindfulness on conflict resolution strategies due to its similar components to the benefits of mindfulness, such as awareness and control of one’s emotions, awareness and understanding of other’s emotions, and cultivation of compassion and empathy. Using a random sampling, 157 participants completed three questionnaires: Five Facet Mindfulness Questionnaire (FFMQ), Trait Emotional Intelligence Questionnaire-Short Form (TEIQue-SF), and Rahim Organizational Conflict Inventory-II (ROCI-II). Utilizing the SPSS Process, results showed a significant relationship between mindfulness and EI. However, among the five approaches to conflict resolution, only the integrating style was significantly related to EI. Following the principle of Mediation Analysis, mindfulness has an indirect effect on integrating style. Moreover, mindfulness and conflict resolution strategies were not significantly related. This is a rather surprising result because research literature has always indicated a positive relationship between the two variables. These findings imply that although integrating style is generally considered the best approach in handling conflict, each style may be appropriate depending on the situation. Mindfulness allows practitioners to have a holistic view of the conflict situation and choose the approach they think best for that specific situation. This could explain why statistically, there is no direct effect of mindfulness on conflict resolution strategies. This work provides basis for the necessity to investigate the factors of conflict instead of the conflict resolution strategies; factors that can be manipulated and may be directly influenced by mindfulness.

Keywords: conflict resolution strategies, emotional intelligence, mindfulness and conflict, ROCI-II integrating style

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3133 Effects of the Supplementary for Understanding and Preventing Plagiarism on EFL Students’ Writing

Authors: Surichai Butcha, Dararat Khampusaen

Abstract:

As the Internet is recognized as a high potential and powerful educational tool to access sources of knowledge, plagiarism is an increasing unethical issue found in students’ writing. This paper is deriving from the 1st phase of an on-going study investigating the effects of the supplementary on citing sources on undergraduate students’ writing. The 40 participants were divided into 1 experimental group and 1 control group. Both groups were administered with a questionnaire on knowledge and an interview on attitude related to using sources in writing. Only the experimental group undertook the 4 lessons focusing on using outside sources and citing the original work (quoting, synthesizing, summarizing and paraphrasing) were delivered to them via e-learning tools throughout a semester. Participants were required to produce 4 writing tasks after each lesson. The results were concerned with types and factors on using outside sources in writing of Thai undergraduate EFL students from the survey. The interview results supported and clarified the survey result. In addition, the writing rubrics confirmed the types of plagiarism frequently occurred in students’ writing. The results revealed the types and factors on plagiarism including their perceptions on using the outside sources in their writing from the interview. The discussion shed the lights on cultural dimensions of plagiarism in student writing, roles of teachers, library, and university policy on the rate of plagiarism. Also, the findings promoted the awareness on ethics in writing and prevented the rate of potential unintentional plagiarism. Additionally, the results of this phase of study could lead to the appropriate contents to be considered for inclusion in the supplementary on using sources for writing for future research.

Keywords: citing source, EFL writing, e-learning, Internet, plagiarism

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3132 International Humanitarian Law and the Challenges of New Technologies of Warfare

Authors: Uche A. Nnawulezi

Abstract:

Undoubtedly, despite all efforts made to achieve overall peace through the application of the principles of international humanitarian law, crimes against mankind which are of unprecedented concern to the whole world have remained unabated. The fall back on war as a technique for settling disputes between nations, individuals, countries and ethnic groups with accompanying toll of deaths and destruction of properties have remained a conspicuous component of human history. Indeed, to control this conduct of warfare and the dehumanization of individuals, a body of law aimed at regulating the impacts of conflicts and hostilities in the theater of war has become necessary. Thus, it is to examine the conditions in which international humanitarian law will apply and also to determine the extent of the challenges of new progressions of warfare that this study is undertaken. All through this examination, we grasped doctrinal approach wherein we used text books, journals, international materials and supposition of law specialists in the field of international humanitarian law. This paper shall examine the distinctive factors responsible for the rebelliousness to the rules of International Humanitarian Law and furthermore, shall proffer possible courses of action that will address the challenges of new technologies of warfare all over the world. Essentially, the basic proposals made in this paper if totally utilized may go far in ensuring a sufficient standard in the application of the rules of international humanitarian law as it relates to an increasingly frequent phenomenon of contemporary developments in technologies of warfare which has in recent past, made it more difficult for the most ideal application of the rules of international humanitarian law. This paper deduces that for a sustainable global peace to be achieved, the rules of International Humanitarian Law as it relates to the utilization of new technologies of warfare should be completely clung to and should be made a strict liability offense. Likewise, this paper further recommends the introduction of domestic criminal law punishment of serious contraventions of the rules of international humanitarian law.

Keywords: international, humanitarian law, new technologies, warfare

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3131 Structural Insulated Panels

Authors: R. Padmini, G. V. Manoj Kumar

Abstract:

Structural insulated panels (SIPs) are a high-performance building system for residential and light commercial construction. The panels consist of an insulating foam core sandwiched between two structural facings, typically oriented strand board (OSB). SIPs are manufactured under factory controlled conditions and can be fabricated to fit nearly any building design. The result is a building system that is extremely strong, energy efficient and cost effective. Building with SIPs will save you time, money and labor. Building with SIPs generally costs about the same as building with wood frame construction when you factor in the labor savings resulting from shorter construction time and less job-site waste. Other savings are realized because smaller heating and cooling systems are required with SIP construction. Structural insulated panels (SIPs) are one of the most airtight and well-insulated building systems available, making them an inherently green product. An airtight SIP building will use less energy to heat and cool, allow for better control over indoor environmental conditions, and reduce construction waste. Green buildings use less energy, reducing carbon dioxide emissions and playing an important role in combating global climate change. Buildings also use a tremendous amount of natural resources to construct and operate. Constructing green buildings that use these resources more efficiently, while minimizing pollution that can harm renewable natural resources, is crucial to a sustainable future.

Keywords: high performance, under factory controlled, wood frame, carbon dioxide emissions, natural resources

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3130 Effect of Particle Size and Concentration of Pomegranate (Punica granatum l.) Peel Powder on Suppression of Oxidation of Edible Plant Oils

Authors: D. G. D. C. L. Munasinghe, M. S. Gunawardana, P. H. P. Prasanna, C. S. Ranadheera, T. Madhujith

Abstract:

Lipid oxidation is an important process that affects the shelf life of edible oils. Oxidation produces off flavors, off odors and chemical compounds that lead to adverse health effects. Chemical mechanisms such as autoxidation, photo-oxidation and thermal oxidation are responsible for lipid oxidation. Refined, Bleached and Deodorized (RBD) coconut oil, Virgin Coconut Oil (VCO) and corn oil are widely used plant oils. Pomegranate fruit is known to possess high antioxidative efficacy. Peel of pomegranate contains high antioxidant activity than aril and pulp membrane. The study attempted to study the effect of particle size and concentration of pomegranate peel powder on suppression of oxidation of RBD coconut oil, VCO and corn oil. Pomegranate peel powder was incorporated into each oil sample as micro (< 250 µm) and nano particles (280 - 300 nm) at 100 ppm and 200 ppm concentrations. The control sample of each oil was prepared, devoid of pomegranate peel powder. The stability of oils against autoxidation was evaluated by storing oil samples at 60 °C for 28 days. The level of oxidation was assessed by peroxide value and thiobarbituric acid reactive substances on 0,1,3,5,7,14 and 28 day, respectively. VCO containing pomegranate particles of 280 - 300 nm at 200 ppm showed the highest oxidative stability followed by RBD coconut oil and corn oil. Results revealed that pomegranate peel powder with 280 - 300 nm particle size at 200 ppm concentration was the best in mitigating oxidation of RBD coconut oil, VCO and corn oil. There is a huge potential of utilizing pomegranate peel powder as an antioxidant agent in reducing oxidation of edible plant oils.

Keywords: antioxidant, autoxidation, micro particles, nano particles, pomegranate peel powder

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3129 Tensile Behavior of Oil Palm Fiber Concrete (OPFC) with Different Fiber Volume

Authors: Khairul Zahreen Mohd Arof, Rahimah Muhamad

Abstract:

Oil palm fiber (OPF) is a fibrous material produced from the waste of palm oil industry which is suitable to be used in construction industry. The applications of OPF in concrete can reduce the material costs and enhance concrete behavior. Dog-bone test provides significant results for investigating the behavior of fiber reinforced concrete under tensile loading. It is able to provide stress-strain profile, modulus of elasticity, stress at cracking point and total crack width. In this research, dog-bone tests have been conducted to analyze total crack width, stress-strain profile, and modulus of elasticity of OPFC. Specimens are in a dog-bone shape with a long notch in the middle as compared to the end, to ensure cracks occur only within the notch. Tests were instrumented using a universal testing machine Shimadzu 300kN, a linear variable differential transformer and two strain gauges. A total of nine specimens with different fibers at fiber volume fractions of 0.75%, 1.00%, and 1.25% have been tested to analyze the behavior under tensile loading. Also, three specimens of plain concrete fiber have been tested as control specimens. The tensile test of all specimens have been carried out for concrete age exceed 28 days. It shows that OPFC able to reduce total crack width. In addition, OPFC has higher cracking stress than plain concrete. The study shows plain concrete can be improved with the addition of OPF.

Keywords: cracks, crack width, dog-bone test, oil palm fiber concrete

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3128 MANIFEST-2, a Global, Phase 3, Randomized, Double-Blind, Active-Control Study of Pelabresib (CPI-0610) and Ruxolitinib vs. Placebo and Ruxolitinib in JAK Inhibitor-Naïve Myelofibrosis Patients

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 200