5,790 research outputs found

    Effects of a physiotherapy and occupational therapy intervention on mobility and activity in care home residents: a cluster randomised controlled trial

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    Objective To compare the clinical effectiveness of a programme of physiotherapy and occupational therapy with standard care in care home residents who have mobility limitations and are dependent in performing activities of daily living

    Detection of activating estrogen receptor gene (ESR1) mutations in single circulating tumor cells

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    Purpose: Early detection is essential for treatment plans before onset of metastatic disease. Our purpose was to demonstrate feasibility to detect and monitor estrogen receptor 1 (ESR1) gene mutations at the single circulating tumor cell (CTC) level in metastatic breast cancer (MBC). Experimental Design: We used a CTC molecular characterization approach to investigate heterogeneity of 14 hotspot mutations in ESR1 and their correlation with endocrine resistance. Combining the CellSearch and DEPArray technologies allowed recovery of 71 single CTCs and 12 WBC from 3 ER-positive MBC patients. Forty CTCs and 12 WBC were subjected to whole genome amplification by MALBAC and Sanger sequencing. Results: Among 3 selected patients, 2 had an ESR1 mutation (Y537). One showed two different ESR1 variants in a single CTC and another showed loss of heterozygosity. All mutations were detected in matched cell-free DNA (cfDNA). Furthermore, one had 2 serial blood samples analyzed and showed changes in both cfDNA and CTCs with emergence of mutations in ESR1 (Y537S and T570I), which has not been reported previously. Conclusions: CTCs are easily accessible biomarkers to monitor and better personalize management of patients with previously demonstrated ER-MBC who are progressing on endocrine therapy. We showed that single CTC analysis can yield important information on clonal heterogeneity and can be a source of discovery of novel and potential driver mutations. Finally, we also validate a workflow for liquid biopsy that will facilitate early detection of ESR1 mutations, the emergence of endocrine resistance and the choice of further target therapy. ©2017 AACR

    Applications of Contaminant Fate and Bioaccumulation Models in Assessing Ecological Risks of Chemicals:  A Case Study for Gasoline Hydrocarbons

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    Mass balance models of chemical fate and transport can be applied in ecological risk assessments for quantitative estimation of concentrations in air, water, soil and sediment. These concentrations can, in turn, be used to estimate organism exposures and ultimately internal tissue concentrations that can be compared to mode-of-action-based critical body residues that correspond to toxic effects. From this comparison, risks to the exposed organism can be evaluated. To illustrate the practical utility of fate models in ecological risk assessments of commercial products, the EQC model and a simple screening level biouptake model including three organisms, (a bird, a mammal and a fish) is applied to gasoline. In this analysis, gasoline is divided into 24 components or ''blocks'' with similar environmental fate properties that are assumed to elicit ecotoxicity via a narcotic mode of action. Results demonstrate that differences in chemical properties and mode of entry into the environment lead to profound differences in the efficiency of transport from emission to target biota. We discuss the implications of these results and insights gained into the regional fate and ecological risks associated with gasoline. This approach is particularly suitable for assessing mixtures of components that have similar modes of action. We conclude that the model-based methodologies presented are widely applicable for screening level ecological risk assessments that support effective chemicals management

    Recognition of specific sialoglycan structures by oral streptococci impacts the severity of endocardial infection.

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    Streptococcus gordonii and Streptococcus sanguinis are primary colonizers of the tooth surface. Although generally non-pathogenic in the oral environment, they are a frequent cause of infective endocarditis. Both streptococcal species express a serine-rich repeat surface adhesin that mediates attachment to sialylated glycans on mucin-like glycoproteins, but the specific sialoglycan structures recognized can vary from strain to strain. Previous studies have shown that sialoglycan binding is clearly important for aortic valve infections caused by some S. gordonii, but this process did not contribute to the virulence of a strain of S. sanguinis. However, these streptococci can bind to different subsets of sialoglycan structures. Here we generated isogenic strains of S. gordonii that differ only in the type and range of sialoglycan structures to which they adhere and examined whether this rendered them more or less virulent in a rat model of endocarditis. The findings indicate that the recognition of specific sialoglycans can either enhance or diminish pathogenicity. Binding to sialyllactosamine reduces the initial colonization of mechanically-damaged aortic valves, whereas binding to the closely-related trisaccharide sialyl T-antigen promotes higher bacterial densities in valve tissue 72 hours later. A surprising finding was that the initial attachment of streptococci to aortic valves was inversely proportional to the affinity of each strain for platelets, suggesting that binding to platelets circulating in the blood may divert bacteria away from the endocardial surface. Importantly, we found that human and rat platelet GPIbα (the major receptor for S. gordonii and S. sanguinis on platelets) display similar O-glycan structures, comprised mainly of a di-sialylated core 2 hexasaccharide, although the rat GPIbα has a more heterogenous composition of modified sialic acids. The combined results suggest that streptococcal interaction with a minor O-glycan on GPIbα may be more important than the over-all affinity for GPIbα for pathogenic effects

    Responses of Bats to Forest Fragmentation in the Mississippi River Alluvial Valley, Arkansas, USA

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    Intense conversion of bottomland hardwood forests to rice and soybeans in the Mississippi River Valley of Arkansas has restricted the remaining forest to isolated fragments. Habitat fragmentation has proven to be detrimental to population sustainability of several species, and is the subject of intense study with often species and latitude specific responses. We compared both coarse land area classes and landscape fragmentation metrics from six 30 km × 30 km subsets centered on publicly owned management areas to bat captures obtained from a 2005 population study. Patch density was the strongest predictor of total captures (R 2 = 0.801, p = 0.016) and of Myotis austroriparius captures (R 2 = 0.856, p = 0.008). Our findings indicate that patch density and area are important predictors of bottomland bat captures

    Toward Realistic Altruism: A Community-Based Field Experience

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    This is a study of the perceptions of preservice teachers engaged in a human services field experience and the college instructors responsible for teaching the Human Development course attached to the field experience. Student data came from semistructured focus group interviews and student journals maintained throughout the experience, faculty data from onc-onone semi-structured interviews. Using the constant comparative method, data for students and faculty were grouped as follows: a) what students do during their placements, b) benefits and challenges of the experience, c) connections built between their experiences in the field and in the classroom. Analysis indicated that while the experience is generally perceived as valuable, there are gaps between what students actually do and faculty perceptions. Also, certain types of placements are much more powerful than others in yielding desired results of empathy, awareness of diversity and teaching skills. Recommendations for increasing the benefits and minimizing knowledge gaps are discussed

    NASA/DOD Aerospace Knowledge Diffusion Research Project. Paper 53: From student to entry-level professional: Examining the technical communications practices of early career-stage US aerospace engineers and scientists

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    Studies indicate that communications and information-related activities take up a substantial portion of an engineer's work week; therefore, effective communications and information-use skills are one of the key engineering competencies that early career-stage aerospace engineers and scientists must possess to be successful. Feedback from industry rates communications and information-use skills high in terms of their importance to engineering practice; however, this same feedback rates the communications and information-use skills of early career-stage engineers low. To gather adequate and generalizable data about the communications and information-related activities of entry-level aerospace engineers and scientists, we surveyed 264 members of the AIAA who have no more than 1-5 years of aerospace engineering work experience. To learn more about the concomitant communications norms, we compared the results of this study with data (1,673 responses) we collected from student members of the AIAA and with data (341 responses) we collected from a study of aerospace engineering professionals. In this paper, we report selected results from these studies that focused on the communications practices and information-related activities of early career-stage U.S. aerospace engineers and scientists in the workplace

    Tourism and the smartphone app: capabilities, emerging practice and scope in the travel domain.

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    Based on its advanced computing capabilities and ubiquity, the smartphone has rapidly been adopted as a tourism travel tool.With a growing number of users and a wide varietyof applications emerging, the smartphone is fundamentally altering our current use and understanding of the transport network and tourism travel. Based on a review of smartphone apps, this article evaluates the current functionalities used in the domestic tourism travel domain and highlights where the next major developments lie. Then, at a more conceptual level, the article analyses how the smartphone mediates tourism travel and the role it might play in more collaborative and dynamic travel decisions to facilitate sustainable travel. Some emerging research challenges are discussed
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