Search results for: Khadijah B. Hashim

Authors: Ahmad Hashim, Thariq Khan Azizuddin Khan, Zulakbal Abd Karim, Nohazira Abdul Karim

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This research aims to obtain the validity and reliability of a survey instrument to evaluate the values, attitudes, and professionalism of sports science students, from the Faculty of Sports Science and Coaching, Universiti Pendidikan Sultan Idris (UPSI). It is a survey which is divided into two components namely first; moral, self-esteem, proactive, self-reliant and voluntary and second; ethics and professionalism. Development of the survey instrument is based on the Malaysian Education Development Plan, Higher Education Malaysia. There are 50 items prepared based on the five-point Likert scale which were tested at the pilot test level. It involved 212 research subjects selected based on random sampling. In addition, the research method applied is in the form of pre-experimental one group pre-test-post-test. Results of the analysis showed that overall field expert validity is r = .89, while the Cronbach alpha reliability correlation value of outdoor education instrument evaluation survey is r = .85. Next, this survey was tested again for construct validity using the factor analysis method for statistical analysis which would validate each item tested was supposed to be in the right component. From the analysis, results show that Bartlett's test is significant p < .05 and Kaiser-Meyer-Olkin index range is r = .87. The result showed 39 survey items are produced out of 50 items of the survey based on this factor analysis method. Research has shown that the survey instrument developed is valid and reliable to be used for the Faculty of Sports Sciences and Coaching, UPSI.

Keywords: values, attitudes, professionalism, ethics, professionalism

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Authors: Hashim Isam Jameel Al-Safi, P. Ranjan Sarukkalige

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Climate change is likely to impact the Australian continent by changing the trends of rainfall, increasing temperature, and affecting the accessibility of water quantity and quality. This study investigates the possible impacts of future climate change on the hydrological system of the Harvey River catchment in Western Australia by using the conceptual modelling approach (HBV mode). Daily observations of rainfall and temperature and the long-term monthly mean potential evapotranspiration, from six weather stations, were available for the period (1961-2015). The observed streamflow data at Clifton Park gauging station for 33 years (1983-2015) in line with the observed climate variables were used to run, calibrate and validate the HBV-model prior to the simulation process. The calibrated model was then forced with the downscaled future climate signals from a multi-model ensemble of fifteen GCMs of the CMIP3 model under three emission scenarios (A2, A1B and B1) to simulate the future runoff at the catchment outlet. Two periods were selected to represent the future climate conditions including the mid (2046-2065) and late (2080-2099) of the 21^st century. A control run, with the reference climate period (1981-2000), was used to represent the current climate status. The modelling outcomes show an evident reduction in the mean annual streamflow during the mid of this century particularly for the A1B scenario relative to the control run. Toward the end of the century, all scenarios show a relatively high reduction trends in the mean annual streamflow, especially the A1B scenario, compared to the control run. The decline in the mean annual streamflow ranged between 4-15% during the mid of the current century and 9-42% by the end of the century.

Keywords: climate change impact, Harvey catchment, HBV model, hydrological modelling, GCMs, LARS-WG

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Authors: A.Halim Sahelan, Mohd Halid Abu, Jamaluddin Hashim, Zulisman Maksom, Mohd Afif Md Nasir

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This study aims to assess the students' needs for the tour planning e-guide. The study is developing on the contribution and importance of the Educational Tour Planning Guide (ETP) is a multimedia courseware as one of the effective methods in teaching and learning of environmental science among the students in primary schools of the Ministry of Education, Malaysia. It is to provide the student with knowledge and experience about tourism, environmental science activities and process. E-guide to ETP also hopes to strengthen the student understanding toward the subject learns in the tourism environmental science. In order to assess the student's needs on the e-Guide to Educational Tour Planning in Environmental Science, the study has produced a similar e-Guide to ETP in the form as a courseware to be tested during the study. The study has involved several steps in order to be completed. It is such as the formulation of the problem, the review of the literature, the formulation of the study methodology, the production of the e-Guide to ETP, field survey and finally the analyses and discussion made on the data gathered during the study. The survey has involved 100 respondents among the students in standard six primary schools in Kluang Johor. Through the findings, the study indicates that the currently tested product is acceptable among the students in learning environmental science as a guide to plan for the tour. The findings also show a slight difference between the respondents who are using the e-Guide to ETP, and those who are not on the basis of the e-Guide to ETP results. Due the important for the study, the researcher hopes to be having a fair discussion and excellence, recommendation for the development of the product of the current study. This report is written also important to provide a written reference for the future related study.

Keywords: the tour planning e-guide, the Educational Tour Planning Guide, environmental science, multimedia course ware

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Authors: Pawthawala Nancy Manish, Syed Alay Hashim

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A hybrid rocket is a rocket engine which uses propellants in two different states of matter- one is in solid and the other either gas or liquid. A hybrid rocket exhibit advantages over both liquid rockets and solid rockets especially in terms of simplicity, stop-start-restart capabilities, safety and cost. This paper deals the design and development of a hybrid rocket having paraffin wax as solid fuel and liquid oxygen as oxidizer. Due to variation of pressure in combustion chamber there is significantly change in mass flow rate, burning rate and uneven regression along the length of the grain. This project describes the working model of a hybrid propellant rocket motor. We have designed a hybrid rocket thrust chamber based on the predetermined combustion chamber pressure and the properties of hybrid propellant. This project is all ready in working condition with normal oxygen injector. Now we have planned to modify the injector design to improve the combustion property. We will use spray type injector for injecting the oxidizer. This idea will increase the performance followed by the regression rate of the solid fuel. By employing mass conservation law, oxygen mass flux, oxidizer/fuel ratio and regression rate the thrust coefficient can be obtained for our current design. CATIA V5 R20 is our design software for the complete setup. This project is fully based on experimental evaluation and the collection of combustion and flow parameters. The thrust chamber is made of stainless steel and the duration of test is around 15-20 seconds (Maximum). These experiments indicates that paraffin based fuel provides the opportunity to satisfy a broad range of mission requirements for the next generation of the hybrid rocket system.

Keywords: burning rate, liquid oxygen, mass flow rate, paraffin wax and sugar

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Authors: N. G. Teik Hiang, Fathyah Hashim

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This is a case of how strategic management techniques can be used to help resolving problems faced by an ageing Small and Medium Enterprise (SME). Strategic way of resolving problems had been proven to be possible in this case despite general thought that strategic management is useful mostly for large corporations. Small and Medium Enterprises (SMEs) can also use strategic management in managing their business and determining their future cause of action and strategies in order to survive in this ever competent world. Strategic orientation is the key to survival and development of small and medium enterprises. In order to adapt to the fierce market competition, ageing SMEs should improve competitiveness and operational efficiency. They must therefore establish a sense of strategic management to improve the strategic management skills, combined with its own unique characteristics, and work out practical strategies to develop core competitiveness of enterprises in the fierce market competition in order to be sustainable. In this case, internal strengths and weaknesses of an SME had been identified. Strategic internal factors and external factors had been classified and further utilized to formulate potential strategies to encounter various problems faced by the SME. These strategies had been further match to take advantages of the opportunities and to overcome the weaknesses and minimize the threats it is facing. Tan, a consultant who was given the opportunity to formulate a plan for the business started with the environmental scanning (internal and external environmental analysis), assessing strengths and weaknesses for the company, strategies generation, analysis and evaluation. He had numerous discussions with the owner of the business and the senior management in order to match the key internal and external factors to formulate alternative strategies for solving the problems that the company facing. Some of the recommendations or solutions are generated from the inspiration of the owner of the business who is a very enterprising and experience businessman.

Keywords: strategic orientation, strategic management, SME, core competitiveness, sustainable

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Authors: Shanti Faridah Salleh, Azzahrah Anuar, Hamimah Ujir, Rohana Sapawi, Wan Hashim Wan Ibrahim, Noraziah Abdul Wahab, Majina Sulaiman, Raudhah Ahmadi, Al-Khalid Othman, Johari Abdullah

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Integrated Cumulative Grade Point Average or iCGPA is an evaluation and reporting system that represents a comprehensive development of students’ achievement in their academic programs. Universiti Malaysia Sarawak, UNIMAS has started its implementation of iCGPA in 2016. iCGPA is driven by the Outcome-Based Education (OBE) system that has been long integrated into the higher education in Malaysia. iCGPA is not only a tool to enhance the OBE concept through constructive alignment but it is also an integrated mechanism to assist various stakeholders in making decisions or planning for program improvement. The outcome of this integrated system is the reporting of students’ academic performance in terms of cognitive (knowledge), psychomotor (skills), and affective (attitude) of which the students acquire throughout the duration of their study. The iCGPA reporting illustrates the attainment of student’s attribute in the eight domains of learning outcomes listed in the Malaysian Qualifications Framework (MQF). This paper discusses on the implementation of iCGPA in UNIMAS on the policy and strategy to direct the whole university to implement the iCGPA. The steps and challenges in integrating the exsting Outcome-Based Education and utilising iCGPA as a tool to quantify the students’ achievement are also highlighted in this paper. Finally, the ACADEMIA system, which is a dedicated centralised program ensure the implementation of iCGPA is a success has been developed. This paper discusses the structure and the analysis of ACADEMIA program and concludes the analysis made on the improvement made on the implementation of constructive alignment in all 40 programs involves in iCGPA implementation.

Keywords: constructive alignment, holistic graduates, mapping of assessment, programme outcome

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Authors: Hamed Karimian, Noraziah Nordin, Mohamad Ibrahim Noordin, Syam Mohan, Mahboubeh Razavi, Najihah Mohd Hashim, Happipah Mohd Ali

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Satureja bachtiarica Bunge is a perennial medicinal plant belonging to the Lamiaceae family and endemic species in Iran. Satureja bachtiarica Bunge with the local name of Marzeh koohi is edible vegetable use as flavoring agent, anti-bacterial and to relieve cough and indigestion. In this study, the anti-cancer effect of Satureja bachtiarica Bunge on the MDA-MB-231 cell line as an Breast cancer cell model has been analyzed for the first time. Satureja bachtiarica Bunge was extracted using different solvents in the order of increasing polarity. Cytotoxicity activity of hexane extract of Satureja bachtiarica Bunge (SBHE) was observed using MTT assay. Acridine orange/Propidium iodide staining was used to detect early apoptosis; Annexin-V-FITC assay was carried out to observe the detection of cell-surface Phosphatidylserine (PS), with Annexin-Vserving as a marker for apoptotic cells. Caspase 3/7, 8 and-9 assays showed significantly activation of caspase-9 where lead intrinsic mitochondrial pathway. Bcl-2/Bax expressions and cell cycle arrest were also investigated. SBHE had exhibited significantly higher cytotoxicity against MDA-MB-231 Cell line compare to other cell lines. A significant increase in chromatin condensation in the cell nucleus was observed by fluorescence analysis. Treatment of MDA-MB-231 cells with SBHE encouraged apoptosis, by down-regulating Bcl-2 and up-regulating Bax, which lead the activation of caspase 9. Moreover, SBHE treatment significantly arrested MDA-MB-231 cells in the G1 phase. Together, the results presented in this study demonstrated that SBHE inhibited the proliferation of MDA-MB-231 cells, leading cell cycle arrest and programmed cell death, which was confirmed to be through the mitochondrial pathway.

Keywords: Satureja bachtiarica Bunge, MDA-MB-231, apoptosis, annexin-V, cell cycle

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Authors: Amanina Iymia Jeffree, Reena Thriumani, Mohammad Iqbal Omar, Ammar Zakaria, Yumi Zuhanis Has-Yun Hashim, Ali Yeon Md Shakaff

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Metabolite profiling is a strategy to be approached in the pattern recognition method focused on three types of cancer cell line that driving the most to death specifically lung, breast, and colon cancer. The purpose of this study was to discriminate the VOCs pattern among cancerous and control group based on metabolite profiling. The sampling was executed utilizing the cell culture technique. All culture flasks were incubated till 72 hours and data collection started after 24 hours. Every running sample took 24 minutes to be completed accordingly. The comparative metabolite patterns were identified by the implementation of headspace-solid phase micro-extraction (HS-SPME) sampling coupled with gas chromatography-mass spectrometry (GCMS). The optimizations of the main experimental variables such as oven temperature and time were evaluated by response surface methodology (RSM) to get the optimal condition. Volatiles were acknowledged through the National Institute of Standards and Technology (NIST) mass spectral database and retention time libraries. To improve the reliability of significance, it is of crucial importance to eliminate background noise which data from 3rd minutes to 17th minutes were selected for statistical analysis. Targeted metabolites, of which were annotated as known compounds with the peak area greater than 0.5 percent were highlighted and subsequently treated statistically. Volatiles produced contain hundreds to thousands of compounds; therefore, it will be optimized by chemometric analysis, such as principal component analysis (PCA) as a preliminary analysis before subjected to a pattern classifier for identification of VOC samples. The volatile organic compound profiling has shown to be significantly distinguished among cancerous and control group based on metabolite profiling.

Keywords: in vitro cancer cell line, metabolite profiling, pattern recognition, volatile organic compounds

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Authors: Farhana Arzu, Roslan Hashim

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Renewable energy is the only alternative sources of energy to meet the current energy demand, healthy environment and future growth which is considered essential for essential sustainable development. Marine renewable energy is one of the major means to meet this demand. Turbines (both horizontal and vertical) play a vital role for extraction of tidal energy. The influence of swept area on the performance improvement of tidal turbine is a vital factor to study for the reduction of relatively high power generation cost in marine industry. This study concentrates on performance investigation of variable length blade tidal turbine concept that has already been proved as an efficient way to improve energy extraction in the wind industry. The concept of variable blade length utilizes the idea of increasing swept area through the turbine blade extension when the tidal stream velocity falls below the rated condition to maximize energy capture while blade retracts above rated condition. A three bladed horizontal axis variable length blade horizontal axis tidal turbine was modelled by modifying a standard fixed length blade turbine. Classical blade element momentum theory based numerical investigation has been carried out using QBlade software to predict performance. The results obtained from QBlade were compared with the available published results and found very good agreement. Three major performance parameters (i.e., thrust, moment, and power coefficients) and power output for different blade extensions were studied and compared with a standard fixed bladed baseline turbine at certain operational conditions. Substantial improvement in performance coefficient is observed with the increase in swept area of the turbine rotor. Power generation is found to increase in great extent when operating at below rated tidal stream velocity reducing the associated cost per unit electric power generation.

Keywords: variable length blade, performance, tidal turbine, power generation

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Authors: Aliyu J. Abubakar, Mazlan Hashim, Amin B. Pour

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Exploiting geothermal resources for either power, home heating, Spa, greenhouses, industrial or tourism requires an initial identification of suitable areas. This can be done cost-effectively using remote sensing satellite imagery which has synoptic capabilities of covering large areas in real time and by identifying possible areas of hydrothermal alteration and minerals related to Geothermal systems. Earth features and minerals are known to have unique diagnostic spectral reflectance characteristics that can be used to discriminate them. The focus of this paper is to investigate the applicability of mapping hydrothermal alteration in relation to geothermal systems (thermal springs) at Yankari Park Northeastern Nigeria, using Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) satellite data for resource exploration. The ASTER Short Wave Infrared (SWIR) bands are used to highlight and discriminate alteration areas by employing sophisticated digital image processing techniques including image transformations and spectral mapping methods. Field verifications are conducted at the Yankari Park using hand held Global Positioning System (GPS) monterra to identify locations of hydrothermal alteration and rock samples obtained at the vicinity and surrounding areas of the ‘Mawulgo’ and ‘Wikki’ thermal springs. X-Ray Diffraction (XRD) results of rock samples obtained from the field validated hydrothermal alteration by the presence of indicator minerals including; Dickite, Kaolinite, Hematite and Quart. The study indicated the applicability of mapping geothermal anomalies for resource exploration in unmapped sparsely vegetated savanna environment characterized by subtle surface manifestations such as thermal springs. The results could have implication for geothermal resource exploration especially at the prefeasibility stages by narrowing targets for comprehensive surveys and in unexplored savanna regions where expensive airborne surveys are unaffordable.

Keywords: geothermal exploration, image enhancement, minerals, spectral mapping

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Authors: Nor Hafizah Selamat, Intan Hashima Mohd Hashim, Noraida Endut, Shariffah Suraya Syed Jamaludin, Sharifah Zahhura Syed Abdullah, Suziana Mat Yasin, Nurul Jannah Ambak

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In Malaysia, report on discrimination against pregnant women at work does exist, and this issue should be taken seriously as large proportion of women in the workforce in Malaysia are of reproductive age. It has been well established that women tend to leave the workforce because of their responsibility in raising the family, to care for family members and, also due to lack of work-life balance. In this case, women find themselves disadvantaged in career and job advancements due to gender roles and expectations connected with maternity. This maternity discrimination have pushed women out of work although The Convention on the Elimination of All Forms of Discrimination Against Women (CEDAW), to which Malaysia is a party, considers discrimination on the ground of maternity is a form of gender discrimination because it hinders women of their effective right to work and requires that special protection be provided for women during maternity to ensure their ability to enjoy the right to work (Article 11(2). What factors prevent women from returning to work and at the same time performing their gender roles expectations? Using semi-structured in-depth interviews this paper explores the experiences of maternity discrimination and their perspectives towards their work employment. 15 women employees who were pregnant or had given birth during her employment period in public and private organizations in Malaysia were participated in this study. While data were analyzed using narrative analysis, respondents were asked on issues related to managing pregnancy, maternity leave and returning to work. The findings revealed that several respondents from private companies stated that they were either dismissed or forced to take unpaid leave due to the company policies. In some cases, respondents also shared how they were treated poorly that they felt that they had to leave their jobs. However, in public organization, the maternity policy implemented showed the support that the employees received from their employer. Study shows that supportive family and employers will encourage employees to return to work. Reasonable adjustments in terms of maternity policies at workplace such as allowing sufficient time in postnatal appointments, offering clear explanation on maternity issues at workplace are something that employees expected from their employers.

Keywords: maternity discrimination, women and work, gender, maternity protection, Malaysia

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Authors: Dalia El Hadi, Alaa Bou Ghannam, Hala Mostafa, Hana Mansour, Ibrahim Hashim, Soubhi Tahhan, Tharwat El Zahran

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Introduction: Neuro-ophthalmological emergencies require prompt assessment and management to avoid vision or life-threatening sequelae. Some would require neuroimaging. Most commonly used are the CT and MRI of the Brain. They can be over-used when not indicated. Their yield remains dependent on multiple factors relating to the clinical scenario. Methods: A retrospective cross-sectional study was conducted by reviewing the electronic medical records of patients presenting to the Emergency Department (ED) with isolated neuro-ophthalmologic complaints. For each patient, data were collected on the clinical presentation, whether neuroimaging was performed (and which type), and the result of neuroimaging. Analysis of the performed neuroimaging was made, and its yield was determined. Results: A total of 211 patients were reviewed. The complaints or symptoms at presentation were: blurry vision, change in the visual field, transient vision loss, floaters, double vision, eye pain, eyelid droop, headache, dizziness and others such as nausea or vomiting. In the ED, a total of 126 neuroimaging procedures were performed. Ninety-four imagings (74.6%) were normal, while 32 (25.4%) had relevant abnormal findings. Only 2 symptoms were significant for abnormal imaging: blurry vision (p-value= 0.038) and visual field change (p-value= 0.014). While 4 physical exam findings had significant abnormal imaging: visual field defect (p-value= 0.016), abnormal pupil reactivity (p-value= 0.028), afferent pupillary defect (p-value= 0.018), and abnormal optic disc exam (p-value= 0.009). Conclusion: Risk indicators for abnormal neuroimaging in the setting of neuro-ophthalmological emergencies are blurred vision or changes in the visual field on history taking. While visual field irregularities, abnormal pupil reactivity with or without afferent pupillary defect, or abnormal optic discs, are risk factors related to physical testing. These findings, when present, should sway the ED physician towards neuroimaging but still individualizing each case is of utmost importance to prevent time-consuming, resource-draining, and sometimes unnecessary workup. In the end, it suggests a well-structured patient-centered algorithm to be followed by ED physicians.

Keywords: emergency department, neuro-ophthalmology, neuroimaging, risk indicators

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Authors: Husam Abdulmuttaleb Hashim

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The environmental pollution problems represent a great challenge to the world, threatening to destroy all the evolution that mankind has reached, the organizations and associations that cares about environment are trying to warn the world from the forthcoming danger resulted from excessive use of nature resources and consuming it without looking to the damage happened as a result of unfair use of it. Most of the urban centers suffers from the environmental pollution problems and health, economic, and social dangers resulted from this pollution, and while the land use planning is responsible for distributing different uses in urban centers and controlling the interactions between these uses to reach a homogeneous and perfect state for the different activities in cities, the occurrence of environmental problems in the shade of existing land use planning operation refers to the disorder or insufficiency in this operation which leads to presence of such problems, and this disorder lays in lack of sufficient importance to the environmental considerations during the land use planning operations and setting up the master plan, so the research start to study this problem and finding solutions for it, the research assumes that using accurate and scientific methods in early stages of land use planning operation will prevent occurring of environmental pollution problems in the future, the research aims to study and show the importance of the environmental impact assessment method (EIA) as an important planning tool to investigate and predict the pollution ranges of the land use that has a polluting pattern in land use planning operation. This research encompasses the concept of environmental assessment and its kinds and clarifies environmental impact assessment and its contents, the research also dealt with urban planning concept and land use planning, it also dealt with the current situation of the case study (Al-Garma district) and the land use planning in it and explain the most polluting use on the environment which is the industrial land use represented in the tannery industries and then there was a stating of current situation of this land use and explaining its contents and environmental impacts resulted from it, and then we analyzed the tests applied by the researcher for water and soil, and perform environmental evaluation through applying environmental impact assessment matrix using the direct method to reveal the pollution ranges on the ambient environment of industrial land use, and we also applied the environmental and site limits and standards by using (GIS) and (AUTOCAD) to select the site of the best alternative of the industrial region in Al-Garma district after the research approved the unsuitability of its current site location for the environmental and site limitations, the research conducted some conclusions and recommendations regard clarifying the concluded facts and to set the proper solutions.

Keywords: EIA, pollution, tannery industry, land use planning

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Authors: Nor Azian Binti Aziz, Muhammad Afiq Bin Tambichik, Zamri Bin Hashim

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The rapid development of the construction industry has contributed to increased construction waste, with concrete waste being among the most abundant. This waste is generated from ready-mix batching plants after the concrete cube testing process is completed and disposed of in landfills, leading to increased solid waste management costs. This study aims to evaluate the engineering characteristics of foamed concrete with waste mixtures construction and agricultural waste to determine the usability of recycled materials in the construction of non-load-bearing walls. This study involves the collection of construction wastes, such as recycled aggregates (RCA) obtained from the remains of finished concrete cubes, which are then tested in the laboratory. Additionally, agricultural waste, such as rice husk ash, is mixed into foamed concrete interlock blocks to enhance their strength. The optimal density of foamed concrete for this study was determined by mixing mortar and foam-backed agents to achieve the minimum targeted compressive strength required for non-load-bearing walls. The tests conducted in this study involved two phases. In Phase 1, elemental analysis using an X-ray fluorescence spectrometer (XRF) was conducted on the materials used in the production of interlock blocks such as sand, recycled aggregate/recycled concrete aggregate (RCA), and husk ash paddy/rice husk ash (RHA), Phase 2 involved physical and thermal tests, such as compressive strength test, heat conductivity test, and fire resistance test, on foamed concrete mixtures. The results showed that foamed concrete can produce lightweight interlock blocks. X-ray fluorescence spectrometry plays a crucial role in the characterization, quality control, and optimization of foamed concrete mixes containing construction and agriculture waste. The unique composition mixer of foamed concrete and the resulting chemical and physical properties, as well as the nature of replacement (either as cement or fine aggregate replacement), the waste contributes differently to the performance of foamed concrete. Interlocking blocks made from foamed concrete can be advantageous due to their reduced weight, which makes them easier to handle and transport compared to traditional concrete blocks. Additionally, foamed concrete typically offers good thermal and acoustic insulation properties, making it suitable for a variety of building projects. Using foamed concrete to produce lightweight interlock blocks could contribute to more efficient and sustainable construction practices. Additionally, RCA derived from concrete cube waste can serve as a substitute for sand in producing lightweight interlock blocks.

Keywords: construction waste, recycled aggregates (RCA), sustainable concrete, structure material

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Authors: Maryam Mohammad Hadi, Heather Nesbitt, Hamzah Masood, Hashim Ahmed, Mark Emberton, John Callan, Alexander MacRobert, Anthony McHale, Nikolitsa Nomikou

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Sonodynamic therapy (SDT) utilises ultrasound in combination with sensitizers, such as porphyrins, for the production of cytotoxic reactive oxygen species (ROS) and the confined ablation of tumours. Ultrasound can be applied locally, and the acoustic waves, at frequencies between 0.5-2 MHz, are transmitted efficiently through tissue. SDT does not require highly toxic agents, and the cytotoxic effect only occurs upon ultrasound exposure at the site of the lesion. Therefore, this approach is not associated with adverse side effects. Further highlighting the benefits of SDT, no cancer cell population has shown resistance to therapy-triggered ROS production or their cytotoxic effects. This is particularly important, given the as yet unresolved issues of radiation and chemo-resistance, to the authors’ best knowledge. Another potential future benefit of this approach – considering its non-thermal mechanism of action – is its possible role as an adjuvant to immunotherapy. Substantial pre-clinical studies have demonstrated the efficacy and targeting capability of this therapeutic approach. However, SDT has yet to be fully characterised and appropriately exploited for the treatment of cancer. In this study, a formulation based on multistimulus-responsive sensitizer-containing nanoparticles that can accumulate in advanced prostate tumours and increase the therapeutic efficacy of SDT has been developed. The formulation is based on a polyglutamate-tyrosine (PGATyr) co-polymer carrying hematoporphyrin. The efficacy of SDT in this study was demonstrated using prostate cancer as the translational exemplar. The formulation was designed to respond to the microenvironment of advanced prostate tumours, such as the overexpression of the proteolytic enzymes, cathepsin-B and prostate-specific membrane antigen (PSMA), that can degrade the nanoparticles, reduce their size, improving both diffusions throughout the tumour mass and cellular uptake. The therapeutic modality was initially tested in vitro using LNCaP and PC3 cells as target cell lines. The SDT efficacy was also examined in vivo, using male SCID mice bearing LNCaP subcutaneous tumours. We have demonstrated that the PGATyr co-polymer is digested by cathepsin B and that digestion of the formulation by cathepsin-B, at tumour-mimicking conditions (acidic pH), leads to decreased nanoparticle size and subsequent increased cellular uptake. Sonodynamic treatment, at both normoxic and hypoxic conditions, demonstrated ultrasound-induced cytotoxic effects only for the nanoparticle-treated prostate cancer cells, while the toxicity of the formulation in the absence of ultrasound was minimal. Our in vivo studies in immunodeficient mice, using the hematoporphyrin-containing PGATyr nanoparticles for SDT, showed a 50% decrease in LNCaP tumour volumes within 24h, following IV administration of a single dose. No adverse effects were recorded, and body weight was stable. The results described in this study clearly demonstrate the promise of SDT to revolutionize cancer treatment. It emphasizes the potential of this therapeutic modality as a fist line treatment or in combination treatment for the elimination or downstaging of difficult to treat cancers, such as prostate, pancreatic, and advanced colorectal cancer.

Keywords: sonodynamic therapy, nanoparticles, tumour ablation, ultrasound

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