1,691 research outputs found

    The aging Canadian population and hospitalizations for acute myocardial infarction: projection to 2020

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    <p>Abstract</p> <p>Background</p> <p>The risk of experiencing an acute myocardial infarction (AMI) increases with age and Canada's population is aging. The objective of this analysis was to examine trends in the AMI hospitalization rate in Canada between 2002 and 2009 and to estimate the potential increase in the number of AMI hospitalizations over the next decade.</p> <p>Methods</p> <p>Aggregated data on annual AMI hospitalizations were obtained from the Canadian Institute for Health Information for all provinces and territories, except Quebec, for 2002/03 and 2009/10. Using these data in a Poisson regression model to control for age, gender and year, the rate of AMI hospitalizations was extrapolated between 2010 and 2020. The extrapolated rate and Statistics Canada population projections were used to estimate the number of AMI hospitalizations in 2020.</p> <p>Results</p> <p>The rates of AMI hospitalizations by gender and age group showed a decrease between 2002 and 2009 in patients aged ≥ 65 years and relatively stable rates in those aged < 64 years in both males and females. However, the total number of AMI hospitalizations in Canada (excluding Quebec) is projected to increase by 4667 from 51847 in 2009 to 56514 in 2020, a 9.0% increase. Inflating this number to account for the unavailable Quebec data results in an increase of approximately 6200 for the whole of Canada. This would amount to an additional cost of between 46and46 and 54 million and sensitivity analyses indicate that it could be between 36and36 and 65 million.</p> <p>Conclusions</p> <p>Despite projected decreasing or stable rates of AMI hospitalization, the number of hospitalizations is expected to increase substantially as a result of the aging of the Canadian population. The cost of these hospitalizations will be substantial. An increase of this extent in the number of AMI hospitalizations and the ensuing costs would significantly impact the already over-stretched Canadian healthcare system.</p

    Serial optical coherence microscopy for label-free volumetric histopathology

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    The observation of histopathology using optical microscope is an essential procedure for examination of tissue biopsies or surgically excised specimens in biological and clinical laboratories. However, slide-based microscopic pathology is not suitable for visualizing the large-scale tissue and native 3D organ structure due to its sampling limitation and shallow imaging depth. Here, we demonstrate serial optical coherence microscopy (SOCM) technique that offers label-free, high-throughput, and large-volume imaging of ex vivo mouse organs. A 3D histopathology of whole mouse brain and kidney including blood vessel structure is reconstructed by deep tissue optical imaging in serial sectioning techniques. Our results demonstrate that SOCM has unique advantages as it can visualize both native 3D structures and quantitative regional volume without introduction of any contrast agents

    Computational modeling of ovarian cancer dynamics suggests optimal strategies for therapy and screening

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    High-grade serous tubo-ovarian carcinoma (HGSC) is a major cause of cancer-related death. Treatment is not uniform, with some patients undergoing primary debulking surgery followed by chemotherapy (PDS) and others being treated directly with chemotherapy and only having surgery after three to four cycles (NACT). Which strategy is optimal remains controversial. We developed a mathematical framework that simulates hierarchical or stochastic models of tumor initiation and reproduces the clinical course of HGSC. After estimating parameter values, we infer that most patients harbor chemoresistant HGSC cells at diagnosis and that, if the tumor burden is not too large and complete debulking can be achieved, PDS is superior to NACT due to better depletion of resistant cells. We further predict that earlier diagnosis of primary HGSC, followed by complete debulking, could improve survival, but its benefit in relapsed patients is likely to be limited. These predictions are supported by primary clinical data from multiple cohorts. Our results have clear implications for these key issues in HGSC management

    American Academy of Optometry Microbial Keratitis Think Tank

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    SIGNIFICANCE Think Tank 2019 affirmed that the rate of infection associated with contact lenses has not changed in several decades. Also, there is a trend toward more serious infections associated with Acanthamoeba and fungi. The growing use of contact lenses in children demands our attention with surveillance and case-control studies. PURPOSE The American Academy of Optometry (AAO) gathered researchers and key opinion leaders from around the world to discuss contact lens-associated microbial keratitis at the 2019 AAO Annual Meeting. METHODS Experts presented within four sessions. Session 1 covered the epidemiology of microbial keratitis, pathogenesis of Pseudomonas aeruginosa, and the role of lens care systems and storage cases in corneal disease. Session 2 covered nonbacterial forms of keratitis in contact lens wearers. Session 3 covered future needs, challenges, and research questions in relation to microbial keratitis in youth and myopia control, microbiome, antimicrobial surfaces, and genetic susceptibility. Session 4 covered compliance and communication imperatives. RESULTS The absolute rate of microbial keratitis has remained very consistent for three decades despite new technologies, and extended wear significantly increases the risk. Improved oxygen delivery afforded by silicone hydrogel lenses has not impacted the rates, and although the introduction of daily disposable lenses has minimized the risk of severe disease, there is no consistent evidence that they have altered the overall rate of microbial keratitis. Overnight orthokeratology lenses may increase the risk of microbial keratitis, especially secondary to Acanthamoeba, in children. Compliance remains a concern and a significant risk factor for disease. New insights into host microbiome and genetic susceptibility may uncover new theories. More studies such as case-control designs suited for rare diseases and registries are needed. CONCLUSIONS The first annual AAO Think Tank acknowledged that the risk of microbial keratitis has not decreased over decades, despite innovation. Important questions and research directions remain

    The development of carbon dots: From the perspective of materials chemistry

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    The advance of materials chemistry has influenced significantly the lifestyle of mankind. By virtue of their fascinating physicochemical nature – including ultrasmall size (<10 nm), rich functional groups, fluorescence, chemical stability, biocompatibility, and nontoxicity – carbon dots have been acclaimed as another epoch-making carbon-based nanomaterial following on from fullerene, nanotubes, and graphene. However, the field of carbon dot-based materials chemistry remains incomplete because of their wide structural diversity, meaning that much fundamental knowledge still needs to be uncovered. Herein, this review proposed several novel viewpoints in term of carbon dot-based material chemistry, including the development history, classification, design principle and applications of carbon dots-based materials. Finally, several sound prospects in this fascinating filed are also given

    How many people have had a myocardial infarction? Prevalence estimated using historical hospital data

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    <p>Abstract</p> <p>Background</p> <p>Health administrative data are increasingly used to examine disease occurrence. However, health administrative data are typically available for a limited number of years – posing challenges for estimating disease prevalence and incidence. The objective of this study is to estimate the prevalence of people previously hospitalized with an acute myocardial infarction (AMI) using 17 years of hospital data and to create a registry of people with myocardial infarction.</p> <p>Methods</p> <p>Myocardial infarction prevalence in Ontario 2004 was estimated using four methods: 1) observed hospital admissions from 1988 to 2004; 2) observed (1988 to 2004) and extrapolated unobserved events (prior to 1988) using a "back tracing" method using Poisson models; 3) DisMod incidence-prevalence-mortality model; 4) self-reported heart disease from the population-based Canadian Community Health Survey (CCHS) in 2000/2001. Individual respondents of the CCHS were individually linked to hospital discharge records to examine the agreement between self-report and hospital AMI admission.</p> <p>Results</p> <p>170,061 Ontario residents who were alive on March 31, 2004, and over age 20 years survived an AMI hospital admission between 1988 to 2004 (cumulative incidence 1.8%). This estimate increased to 2.03% (95% CI 2.01 to 2.05) after adding extrapolated cases that likely occurred before 1988. The estimated prevalence appeared stable with 5 to 10 years of historic hospital data. All 17 years of data were needed to create a reasonably complete registry (90% of estimated prevalent cases). The estimated prevalence using both DisMod and self-reported "heart attack" was higher (2.5% and 2.7% respectively). There was poor agreement between self-reported "heart attack" and the likelihood of having an observed AMI admission (sensitivity = 63.5%, positive predictive value = 54.3%).</p> <p>Conclusion</p> <p>Estimating myocardial infarction prevalence using a limited number of years of hospital data is feasible, and validity increases when unobserved events are added to observed events. The "back tracing" method is simple, reliable, and produces a myocardial infarction registry with high estimated "completeness" for jurisdictions with linked hospital data.</p

    Against quantiles: categorization of continuous variables in epidemiologic research, and its discontents

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    <p>Abstract</p> <p>Background</p> <p>Quantiles are a staple of epidemiologic research: in contemporary epidemiologic practice, continuous variables are typically categorized into tertiles, quartiles and quintiles as a means to illustrate the relationship between a continuous exposure and a binary outcome.</p> <p>Discussion</p> <p>In this paper we argue that this approach is highly problematic and present several potential alternatives. We also discuss the perceived drawbacks of these newer statistical methods and the possible reasons for their slow adoption by epidemiologists.</p> <p>Summary</p> <p>The use of quantiles is often inadequate for epidemiologic research with continuous variables.</p

    Adaptive targeting for online advertisement

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    We consider the problem of adaptive targeting for real-time bidding for internet advertisement. This problem involves making fast decisions on whether to show a given ad to a particular user. For intelligent platforms, these decisions are based on information extracted from big data sets containing records of previous impressions, clicks and subsequent purchases. We discuss several strategies for maximizing the click through rate, which is often the main criteria of measuring the success of an advertisement campaign. In the second part of the paper, we provide some results of statistical analysis of real data

    Coevolved mutations reveal distinct architectures for two core proteins in the bacterial flagellar motor

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    Switching of bacterial flagellar rotation is caused by large domain movements of the FliG protein triggered by binding of the signal protein CheY to FliM. FliG and FliM form adjacent multi-subunit arrays within the basal body C-ring. The movements alter the interaction of the FliG C-terminal (FliGC) "torque" helix with the stator complexes. Atomic models based on the Salmonella entrovar C-ring electron microscopy reconstruction have implications for switching, but lack consensus on the relative locations of the FliG armadillo (ARM) domains (amino-terminal (FliGN), middle (FliGM) and FliGC) as well as changes during chemotaxis. The generality of the Salmonella model is challenged by the variation in motor morphology and response between species. We studied coevolved residue mutations to determine the unifying elements of switch architecture. Residue interactions, measured by their coevolution, were formalized as a network, guided by structural data. Our measurements reveal a common design with dedicated switch and motor modules. The FliM middle domain (FliMM) has extensive connectivity most simply explained by conserved intra and inter-subunit contacts. In contrast, FliG has patchy, complex architecture. Conserved structural motifs form interacting nodes in the coevolution network that wire FliMM to the FliGC C-terminal, four-helix motor module (C3-6). FliG C3-6 coevolution is organized around the torque helix, differently from other ARM domains. The nodes form separated, surface-proximal patches that are targeted by deleterious mutations as in other allosteric systems. The dominant node is formed by the EHPQ motif at the FliMMFliGM contact interface and adjacent helix residues at a central location within FliGM. The node interacts with nodes in the N-terminal FliGc α-helix triad (ARM-C) and FliGN. ARM-C, separated from C3-6 by the MFVF motif, has poor intra-network connectivity consistent with its variable orientation revealed by structural data. ARM-C could be the convertor element that provides mechanistic and species diversity.JK was supported by Medical Research Council grant U117581331. SK was supported by seed funds from Lahore University of Managment Sciences (LUMS) and the Molecular Biology Consortium
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