Developing fixed dose combinations for the geriatric population

Background: Successful therapeutic outcomes demand a patient’s adherence to their dosage regimen, yet this is challenging to achieve among elderly people on multidrug therapies (polypharmacy). Therefore, it is the task of formulators to prepare medicines to minimise the burden on patients and maximise the likelihood of a dosage regimen being accurately followed. One route to improve adherence rates is to prepare fixed-dose-combinations (FDCs), in which multiple active ingredients are loaded into a single formulation. This thesis aims to develop different FDCs of multiple drug-polymer composite systems targeting specific conditions for the geriatric population utilising advanced pharmaceutical manufacturing techniques. Methods: Different biocompatible polymers were selected for each formulation based on dissolution behaviour in aqueous media. The polymers were mixed with the selected combination of drugs and then formulated. Initially, fast-dissolving materials based on poly(vinylpyrrolidone) (PVP) were generated by either film casting (a conventional technique used to prepare orodispersible films), or single-needle electrospinning (to prepare FDCs in the form of nanoscale fibres). Further modification of the electrospinning setup was then undertaken to prepare oral FDCs containing ibuprofen, famotidine, and prednisone. Three polymers (PVP, Eudragit-L100, and Eudragit-RSPO) were used to generate fibres, and sequential and multi-jet electrospinning employed to fabricated FDCs. Finally, core/shell fibres made of Eudragit-RLPO/PVP, as a platform for levodopa and carbidopa both equally loaded in each layer of the core and shell, for biphasic release oral FDCs was performed using coaxial electrospinning. Results: FDC in the form of PVP-based fast-dissolving oral films loaded with amlodipine besylate and valsartan were prepared by film casting between 5-30% w/w and electrospinning between 5-55% w/w. A comparison between the two types of formulations showed that 90% drug release could be achieved from the electrospun fibres within 2 minutes, while the cast film ODFs took 6 minutes. Next oral FDCs prepared from ibuprofen, famotidine, and prednisone proved the ability to generate different FDCs through modification of electrospinning setup by sequential and multi-jet electrospinning. Results from the in vitro drug release studies showed that the desired multi-phasic drug release could be obtained. This began with the immediate release of drug-loaded in the PVP layer instantly within ~1hr of sampling, followed by release from the Eudragit-L100 fibres triggered by the change of pH >6, and finally extended-release from the Eudragit-RSPO fibres to reach >80% after ~16 hours. Last FDC, the core/shell fibres gave similar release profiles for levodopa and carbidopa, with 50% immediate release from the PVP compartment, followed by 50% extended-release from Eudragit-RLPO. Overall the formulation provided the desired biphasic release profile. Conclusions: The appropriate selection of polymer and manufacturing technique, can fabricate effective drug-polymer composite systems for multiple drug delivery via FDCs. Ultimately, it is believed these could be applied to enhance patient adherence

Fabrication of Electrospun Levodopa-Carbidopa Fixed-Dose Combinations

We report in this work coaxial electrospun fibers with potential applications in the treatment of Parkinson’s disease. The fibers comprise a fixed dose combination (FDC) containing the active ingredients levodopa and carbidopa, loaded in a fast dissolving polyvinylpyrrolidone (PVP) shell and an insoluble but swellable Eudragit® RLPO core. Under appropriate processing conditions we are able to prepare fibers with distinct core/shell architectures and diameters of approximately 400 nm. X-ray diffraction and differential scanning calorimetry analyses revealed that the drugs are dispersed on the molecular level within the polymer carriers, and IR spectroscopy indicated the presence of intermolecular interactions. At pH 1, the composite fibers yields extended release over more than 8 h, with an initial loading dose being freed from the PVP shell and then a sustained release phase following from the insoluble core. This is markedly extended over the release period of the commercial FDC product, and thus the fibers generated here have the potential to be used to reduce the required dosing frequency

Solid waste management in Dhaka

Solid waste management in Dhak

An Open-Domain Question Answering System Using Annotated Web Feeds.

Open Domain Question Answering Systems (ODQA) aim to answer all possible questions, regardless of topic and time. For this to be possible, most current ODQA systems depend on the World Wide Web through search engines, e.g. Google, which provide an abundance of information. Problem arises when search engines require a few days to crawl, archive and index the latest documents depending on the popularity of the website and the search engine's indexing efficiency. Thus, recent information may not be available as soon as it is published. Our work focuses on capturing and populating current news articles from various trusted resources into a single unified repository. We have implemented a prototype which uses Web 2.0 RSS feed technology to capture the information. This includes an interface which allows other question answering systems to access our repository using various formats' e.g. XML and SQL query. We have also implemented a question answering engine which employs keyword detection, query expansion and rule matching

BIM: Integrating Cost Estimates at Initial/Design Stage

The accuracy of the cost estimates is very important in the initial stage because it will determine the viability of the project and provide the project budget. Therefore, Inaccuracy of the cost estimates beyond the acceptable range will cause the cost overrun in the later stage. This research aims to recommend BIM to be applied as a part of the cost management process and to improve the cost estimating at the initial/design stage. In addition, this research will investigate the factors influencing the accuracy, why BIM not been applied to reduce the inaccuracy and how BIM can be integrated into cost estimates at the initial / design stage. This research was carried out via literature review, questionnaire survey and semi-structured interview. It was indicated that insufficient information related to the project, poor communication between project team and complexity of design and construction are the three most factors influenced the accuracy of cost estimates. While collaborating and sharing information between the project team, and investment in software and training are the barriers in implementing BIM. The research also found out that BIM is an integrated multi-disciplinary tool that serves architecture, structural and M&E. In addition, the capability of BIM in assisting cost estimates allow QS to focus more value adding activities in estimating such as: identifying construction assemblies, pricing and factoring risks, which are essential for high quality estimates. In conclusion, with the capability of BIM and its integration will help to minimize the error and enhance the project cost estimates in the future

The role of E-cadherin in modulating the behaviour characteristics of oral squamous carcinoma cells.

The incipient invasion of epithelial tumour cells, characterised by disruption of normal cell-cell adhesion, marks the point of transition to malignancy. C-adherins are a family of calcium-dependent, transmembrane, cell-cell adhesion molecules whose function requires association with the actin cytoskeleton of the cell through cytoplasmic proteins called catenins. Oral keratinocytes express E-cadherin, which is considered a regulator of the epithelial phenotype. Loss of E-cadherin commonly is seen in oral squamous cell carcinoma (OSCC), particularly in poorly differentiated tumours, allowing cells to detach from the tumour mass, invade and metastasise. An E-cadherin negative OSCC cell line was identified where E-cadherin expression and function was restored through cDNA transfection resulting in functional cell surface expression of the protein and the formation of cell-cell attachments, with significant alteration in levels and distribution of catenins. Alteration of cell morphology, from a spindle to an epitheloid form, was observed. Additionally, restoration of E-cadherin showed a marked inhibition of the invasive potential of this OSCC cell line. These effects were not observed in the control cell line transfected with the expression vector containing antisense E-cadherin cDNA. Most findings in cell and molecular biology, presented in the literature, are based, primarily, on in vitro studies obtained from the culture of cells growing in 2-dimensional (2-D) tissue culture dishes. In this study I have investigated if E-cadherin plays a role in modulating tumour cell growth in a 3-D, as opposed to a 2-D, environment. Results showed that the epitheloid-like morphology brought about by E-cadherin expression under 2-D conditions allows differences in density dependent inhibition to occur accompanied by enhancement in the apoptotic capacity of the cells. However, where constraints of 3-D culture are imposed, these variations between E-cadherin expressing and non-expressing lines disappear. To explore the basis of these changes I have examined Western blot analysis of proteins known to play a role in mediating cell proliferation or regulation of apoptosis, such as Bcl-2, Akt-1, ILK and N-cadherin. I showed that changes in levels of expression of these proteins under 2-D conditions is markedly affected when cells were implanted in 3-D collagen I cultures. I also investigated the possible molecular cross talk between E-cadherin and the (34-integrin subunit. Results obtained from (34-knock-down experiments showed that (iH-integrin plays a role in the maturation of E-cadherin-dependent cell-cell contacts. I investigated the possible mechanisms of this apparent cadherin-integrin cross-talk and preliminary results showed that the function of (34-integrin was, potentially, executed through the Racl small Rho GTPase

Effect of Health Education on Raising Female Students Awareness' Regarding Breast Cancer at Saudi Arabia

Breast cancer is a major killer in women globally and in developing regions where the early cancer detection facilities are unavailable, with late presentation and prognosis is worse. Breast cancer awareness would be a tool to fight this disease through early detection and there by decrease the morbidity and mortality. Aim of the study: to improve female students’ knowledge and practice toward breast cancer in Saudi Arabia. Methodology: Research Design: A quasi experimental design was used. Tools: Three tools were developed for data collection including interviewing questionnaire which include socio-demographic characteristics, female students attitude toward breast cancer and source of their knowledge about breast cancer, students’ knowledge assessment sheet about risk factors, signs, symptoms and screening of breast cancer, and the third tool was about the practice of breast self –examination. Sample: a convenient sample of 339 female students was recruited in this study. The data collection was from February to end May2013. Results: Data were collected from 339 female students. About 69.9% of students in the age group from 20-22 years. There were statistically significant improvements of students’ knowledge score after education regarding risk factors, signs and symptoms, and screening of breast cancer. Additionally 17.1% of students were practicing breast self examination (BSE) in pretest compared to 35.4% of them in posttest. Conclusion: Post educational sessions not only improved female students’ knowledge but also, significantly improved the attitude toward breast cancer self examination. Keywords: Breast Cancer, Breast Self Examination, Screening of  Breast Cancer, Raising Awareness

Perancangan tokoh Bubu dan MadBull pada Film Animasi 2D "Petualangan si Bubu"

Character design in animation film is very important. In designing a character must have fix concept in order to be able to show the personality, background, and also the uniqueness of the character who has differences from the other characters that can attract the attention and curiosity of the audience on that animation film. The character of this animation films is very diverse, with the emergence of new animations that is reference in making new character. This research was conducted by the author aimed to design Bubu and MadBull figures. Bubu plays the protagonist, and MadBull play the antagonist, that found in this 2D animation film with tittle “Petualangan si Bubu”

The role of knowledge artefact and agency in IS project escalation

This research contributes to current academic thinking by highlighting new perspective to studying the IS Project Escalation phenomenon through the application of Agency Theory. This theory views the customer as the (principal) who needs an IS product, and the IS developer as the (agent) who creates this IS product. According to this viewpoint, examining current IS project escalation literature suggests the majority of previous studies implicitly adopted the assumption that the customer (principal) is entirely capable of identifying the requirements of the proposed IS product, and a project is prone to escalate because of the attitude of the IS developer (agent). This presents a gap in the literature in that the impact of the customer (principal) not been explicitly explored. As such, one critical aim of this research is to investigate IS project escalation by employing an extension of Agency Theory. This extended theory assumes that the customer (principal) suffers challenges of incompetence when it comes to the transfer of knowledge (i.e. requirements) to the IS developer (agent). This leads to a situation of information asymmetry on the principal’s side because of incomplete knowledge transfer. In turn, this situation develops and leads to IS project escalation. Another aim of this research is to investigate the process of requirement elicitation (RE) in IS development practice. This is to identify the role of the incorporated knowledge artefacts within this activity, in terms of how the project manager and developers effectively create and utilise these objects. Thus, this is in order to provide a possible solution with respect to the challenge of incomplete knowledge transfer. To achieve that, this research employed a qualitative methodology and collected data in two stages in Saudi Arabia by using semi-structured interviews. In this respect, in the first stage, a number interviews with 30 IS project manager form five different IS development organisations is conducted. In the second stage, a number of interviews with 10 customers form different organisations is conducted. The findings in general acknowledged and complemented a number of previous studies’ results through the employed perspective of the extended Agency Theory in this research. Considering the identified gap, the empirical evidence supported the assumption of this research, and provided a new explanation for IS project escalation which highlighted the role of the customer (principal) this time. In addition, an influence diagram (i.e. Project Escalation Framework), which clarifies the relationship between the reasons behind incomplete knowledge transfer and IS project escalation, is developed. Also, the empirical evidence identifies a number of incorporated and relevant knowledge artefacts throughout the process of requirement elicitation (RE), namely Initial Request, Features, Process Diagrams, Prototypes, and Requirements. In this respect, the discussion categorised the different roles these artefacts can act out, in terms of being boundary object, epistemic objects, and activity objects. Additionally, a process diagram (i.e. Knowledge Transfer Framework), which clarifies the knowledge process in five main steps during RE phase, is developed. Analysing a number of IS development cases in a various contexts demonstrated multiple practical applications of the Project Escalation Framework with respect to managing issues building up to and leading to several project outcomes (i.e. success, failure, and escalation). Additionally, this analysis presented the artefacts in the Knowledge Transfer Framework as critical linchpins of an otherwise fragmented process when it comes to eliciting customer requirements. These artefacts have much broader implications that go beyond acting as just a procedure to elicit customer requirements. The ‘inclusion’ or ‘omission’ of these artefacts contributes to project success or failure respectively. Consequently, this understanding will result in improvement of IS development investigations, rather than exclusively enhance RE processes between principals and agents. Furthermore, the findings provided a number of highlighted things to be aware of and useful hints which reflect professional experience from real life applications. Thus, considering learning from such rich experience in terms of employing the advantages and avoiding the drawbacks would positively reflect on IS development practice. This includes managing and dealing with challenges of IS development projects, particularly project escalation, in addition to improving RE process and enhancing the process of receiving customer requirements and ideas

Incorporating the Oceanic-Atmospheric Climate Variables to Enhance Streamflow Reconstruction Skill

Streamflow is a vital source of water supply. Information about the historic streamflow helps understand the range of climate variability and develop sustainable water management strategies for the future. The available instrumental data is usually limited and thus might be insufficient to describe the long-term hydrologic patterns of a region. Streamflow reconstruction, by increasing the length of the hydrologic data, is an important tool to understand past hydrology