175 research outputs found

    Scoping Review on Homelessness in Canada

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    According to a 2020 Nanos Research poll commissioned by the Canadian Alliance to End Homelessness, 72 percent of Canadians believe that ending homelessness should be one of the country\u27s top priorities. Given that homelessness is a social crisis, it is important to establish what is currently known about the situation in order to develop innovative and effective solutions. While some studies have reviewed homeless for specific sub-populations such as street youth and homeless families, few have conducted a comprehensive large-scale scan of the literature pertaining to homelessness in Canada. Additionally, hardly any studies have examined how homelessness is measured in Canadian datasets from government agencies and homeless organizations. For these reasons, this study offers a scoping review of both the peer-reviewed academic research on homelessness in Canada and the homeless datasets provided by government institutions and private organizations. The purpose of this report is to present an overview of the existing literature and databases on homelessness in Canada, as well as highlight relevant data gaps that must be addressed in future studies

    Cationic gold(I) heteroleptic complexes bearing a pyrazole-derived N-heterocyclic carbene: syntheses, characterizations, and cytotoxic activities

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    10.1039/c3dt51071aDalton Transactions423412421-1242

    Targeted Stimuli-Responsive Dextran Conjugates for Doxorubicin Delivery to Hepatocytes

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    A targeted, stimuli-responsive, polymeric drug delivery vehicle is being developed in our lab to help alleviate severe side-effects caused by narrow therapeutic window drugs. Targeting specific cell types or organs via proteins, specifically, lectin-mediated targeting holds potential due to the high specificity and affinity of receptor-ligand interactions, rapid internalization, and relative ease of processing. Dextran, a commercially available, biodegradable polymer has been conjugated to doxorubicin and galactosamine to target hepatocytes in a three-step, one-pot synthesis. The loading of doxorubicin and galactose on the conjugates was determined by absorbance at 485 nm and elemental analysis, respectively. Conjugation efficiency based on the amount loaded of each reactant varies from 20% to 50% for doxorubicin and from 2% to 20% for galactosamine. Doxorubicin has also been attached to dextran through an acid-labile hydrazide bond. Doxorubicin acts by intercalating with DNA in the nuclei of cells. The fluorescence of doxorubicin is quenched when it binds to DNA. This allows a fluorescence-based cell-free assay to evaluate the efficacy of the polymer conjugates where we measure the fluorescence of doxorubicin and the conjugates in increasing concentrations of calf thymus DNA. Fluorescence quenching indicates that our conjugates can bind to DNA. The degree of binding increases with polymer molecular weight and substitution of doxorubicin. In cell culture experiments with hepatocytes, the relative uptake of polymer conjugates was evaluated using flow cytometry, and the killing efficiency was determined using the MTT cell proliferation assay. We have found that conjugate uptake is much lower than that of free doxorubicin. Lower uptake of conjugates may increase the maximum dose of drug tolerated by the body. Also, non-galactosylated conjugate uptake is lower than that of the galactosylated conjugate. Microscopy indicates that doxorubicin localizes almost exclusively at the nucleus, whereas the conjugates are present throughout the cell. Doxorubicin linked to dextran through a hydrazide bond was used to achieve improved killing efficiency. Following uptake, the doxorubicin dissociates from the polymer in an endosomal compartment and diffuses to the nucleus. The LC₅₀ of covalently linked doxorubicin is 7.4 μg/mL, whereas that of hydrazide linked doxorubicin is 4.4 μg/mL.Singapore-MIT Alliance (SMA

    Control and modeling of underwater flexible manipulator structure

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    The use of flexible structures in many engineering applications is expanding rapidly. Position control is delicate, such as angular position control of a flexible structure especially underwater condition. Flexible structure in an underwater condition often having the problem of the hub angle position as the hub angle is affected by the inline force of the flexible structure underwater. To develop an optimum control system for the horizontal motion of such condition, the operating system must first be identified. A system model of an experimental test rig representing the Underwater Flexible Single Link Manipulator System (UFSLMS), needs to be developed before designing a controller to control the hub angle position. The objectives of this project are to identify the model and develop the controller to control the hub angle position of a UFSLMS. Previous studies have shown that parametric modelling involving Auto Regressive with Exogenous Input model using Recursive Least Squares algorithm, and non-parametric modelling involving Evolution Algorithm are suitable to model the UFSLMS system, with acceptably low Mean Square Error. The project is done by reviewing the UFSLMS dynamic modelling and control methodology. The collection of data from the UFSLMS system will be simulated and identified as the dynamic UFSLMS. A Proportional- Integral-Derivative controller is developed based on the system identification model, using heuristic techniques within MATLAB environment and robustness test is carried out at different magnitudes to determine the robustness of the controller. The performance of the controllers thus developed is verified and validated by simulation on MATLAB SIMULINK. The objectives are achieved when the controller is proven to be stable by effectively control the hub angle position in the horizontal motion underwater

    Utility of routine screening for alpha-1 antitrypsin deficiency in patients with bronchiectasis

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    Alpha-1 antitrypsin deficiency (AATD) is a cause of bronchiectasis. Guidelines for bronchiectasis from the British Thoracic Society do not recommend to routinely test patients for AATD. In contrast, guidelines for AATD recommend routine screening. This contradiction, in part, results from the lack of data from large studies performing comprehensive screening. We screened 1600 patients with bronchiectasis at two centres in the UK from 2012 to 2016. In total, only eight individuals with AATD were identified representing 0.5% of the overall population. We conclude that routine screening for AATD in bronchiectasis in the UK has a low rate of detection. Further studies are required in different geographical regions, which may have a higher prevalence of AATD.info:eu-repo/semantics/publishedVersio

    Targeted Stimuli-Responsive Dextran Conjugates for Doxorubicin Delivery to Hepatocytes

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    A targeted, stimuli-responsive, polymeric drug delivery vehicle has been developed to help alleviate the severe side-effects caused by narrow therapeutic window drugs. Doxorubicin, a commonly used chemotherapeutic agent has been conjugated to dextran by two different techniques. In the first method, doxorubicin and hepatocyte-targeting galactosamine were attached to dextran through amine bonds. Conjugation efficiency based on the amount loaded of each reactant varied from 1% to 50% for doxorubicin and from 2% to 20% for galactosamine, depending on various synthesis parameters. For the second conjugate, doxorubicin was attached to dextran through an acid-labile hydrazide bond. Fluorescence quenching indicated that all our conjugates can bind to DNA. The degree of binding was improved with increasing polymer molecular weight and substitution of doxorubicin, and also with hydrazide-bonded conjugate. In cell culture experiments, we have found that the uptake of conjugates was much lower than that of free doxorubicin. Lower uptake of conjugates decreased the toxicity of doxorubicin. Also, the uptake of non-galactosylated conjugate was lower than that of the galactosylated conjugate. Microscopy studies indicated that doxorubicin was localized almost exclusively at the nucleus, whereas the amine-bonded conjugates were present throughout the cell. Targeted amine-linked conjugates and hydrazide-bonded conjugates achieved greatly improved cytotoxicity. Following uptake, the doxorubicin was dissociated from the hydrazide conjugate in an endosomal compartment and diffused to the nucleus. The LC₅₀ values of non-targeted amine-linked, targeted amine-linked, and hydrazide-linked doxorubicin were 19.81 μg/mL, 7.33 μg/mL and 4.39 μg/mL, respectively. The amine-linked conjugates were also tested on a multidrug-resistant cell line; the LC₅₀ values of doxorubicin and the non-targeted amine-linked conjugate were 8.60 μg/mL and 36.02 μg/mL, respectively.Singapore-MIT Alliance (SMA

    The Query Cube: A Framework for Assessing User Productivity with Database Information Retrieval

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    Three key factors that affect user productivity on database information retrieval are representation realism, expressive ease, and task complexity. Representation realism is the level of abstraction used in formulating queries. Expressive ease is the syntactic flexibility of a query language. Task complexity is the level of difficulty of queries. These factors formed a three dimensional query cube. A laboratory experiment was conducted to evaluate user productivity on database information retrieval corresponding to different vertices of the query cube. The results show that the query cube is a viable framework for assessing user productivity, both on effectiveness and efficiency perspective

    Men’s perceptions and preferences regarding prostate cancer radiation therapy: A systematic scoping review

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    Purpose: To assess the literature on men’s preferences and perceptions regarding prostate cancer radiation therapy. Methods: A scoping review was undertaken as per JBI guidelines. Searches were conducted in PubMed, CINAHL, Scopus and Science Direct with search terms including “prostate cancer,” “radiotherapy,” “radiation therapy,” “radiation oncology,” “patient preferences,” “patient perceptions” and “patient experience.” The resultant studies were mapped and grouped according to the emergent themes and pathway stages. Results: A total of 779 titles and abstracts were screened by two independent reviewers. Fifty-two full-text studies were reviewed, with 27 eligible for inclusion. There were 4 pre-treatment, 13 during treatment and 10 post-treatment studies covering broad themes of information needs (n = 3), preferences and decisions (n = 6), general experiences (n = 8), side effects (n = 6), and support (n = 4). There were a mix of methodologies, including 11 qualitative, 14 quantitative (including four preference studies), one mixed methods and one narrative review. Conclusion: There were only four preference studies, with the remaining 23 reporting on perceptions. Overall, there is a paucity of literature regarding patient preferences and perceptions of prostate cancer radiation therapy, particularly when considering how many clinical and technical studies are published in the area. This highlights opportunities for future research

    Multiplexable fluorescence lifetime imaging (FLIM) probes for Abl and Src-family kinases

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    Many commonly employed strategies to map kinase activities in live cells require expression of genetically encoded proteins (e.g. FRET sensors). In this work, we describe the development and preliminary application of a set of cell-penetrating, fluorophore labelled peptide substrates for fluorescence lifetime imaging (FLIM) of Abl and Src-family kinase activities. These probes do not rely on FRET pairs or genetically-encoded protein expression. We further demonstrate probe multiplexing and pixel-by-pixel quantification to estimate the relative proportion of modified probe, suggesting that this strategy will be useful for detailed mapping of single cell and subcellular dynamics of multiple kinases concurrently in live cells
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