2,961 research outputs found

    Mycobacterium tuberculosis infection induces non-apoptotic cell death of human dendritic cells

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    <p>Abstract</p> <p>Background</p> <p>Dendritic cells (DCs) connect innate and adaptive immunity, and are necessary for an efficient CD4<sup>+ </sup>and CD8<sup>+ </sup>T cell response after infection with <it>Mycobacterium tuberculosis </it>(Mtb). We previously described the macrophage cell death response to Mtb infection. To investigate the effect of Mtb infection on human DC viability, we infected these phagocytes with different strains of Mtb and assessed viability, as well as DNA fragmentation and caspase activity. In parallel studies, we assessed the impact of infection on DC maturation, cytokine production and bacillary survival.</p> <p>Results</p> <p>Infection of DCs with live Mtb (H37Ra or H37Rv) led to cell death. This cell death proceeded in a caspase-independent manner, and without nuclear fragmentation. In fact, substrate assays demonstrated that Mtb H37Ra-induced cell death progressed without the activation of the executioner caspases, 3/7. Although the death pathway was triggered after infection, the DCs successfully underwent maturation and produced a host-protective cytokine profile. Finally, dying infected DCs were permissive for Mtb H37Ra growth.</p> <p>Conclusions</p> <p>Human DCs undergo cell death after infection with live Mtb, in a manner that does not involve executioner caspases, and results in no mycobactericidal effect. Nonetheless, the DC maturation and cytokine profile observed suggests that the infected cells can still contribute to TB immunity.</p

    Recommending anchor points in structure-preserving hypertext document retrieval

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    Traditional WWW search engines index and recommend individual Web pages to assist users in locating relevant documents. Users are often overwhelmed by the large answer set recommended by the search engines. The logical starting point of the hyper-document is thus hidden among the large basket of matching pages. Users need to spend a lot of effort browsing through the pages to locate the starting point, a very time consuming process. This paper studies the anchor point indexing problem. The anchor points of a given user query is a small set of key pages from which the larger set of documents that are relevant to the query can be easily reached. The use of anchor points help solve the problems of huge answer set and low precision suffered by most search engines by considering the hyper-link structures of the relevant documents, and by providing a summary view of the result set.published_or_final_versio

    Exercise intervention and sexual function in advanced prostate cancer: a randomised controlled trial.

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    ObjectivesTreatments for prostate cancer such as androgen deprivation therapy (ADT), surgery and radiation therapy can adversely affect sexual, urinary and bowel function. Preliminary research has demonstrated the efficacy of exercise to preserve sexual function in men with localised prostate cancer receiving ADT, though this has yet to be investigated in a metastatic setting. We examined the effects of a 12-week exercise programme comprising resistance, aerobic and flexibility training on sexual health and function in men with advanced prostate cancer.MethodsPatients with prostate cancer (70.0±8.4 year; body mass index 28.7±4.0 kg/m2) with bone metastases (rib/thoracic spine, 66.7%; lumbar spine, 43.9%; pelvis, 75.4%; femur, 40.4%; humerus, 24.6%; other sites, 70.2%) were randomly assigned to supervised exercise 3 days/week (n=28) or usual care (n=29). Sexual health and function were assessed using the International Index of Erectile Function, the Expanded Prostate Cancer Index Composite and the EORTC-PR25 at baseline and 12 weeks.ResultsPatients attended 89% of planned sessions and there were no adverse events. After adjusting for baseline values, there was no significant difference between groups for any measure of sexual function and activity (p>0.05). Additionally, there was no significant difference between groups for urinary and bowel function assessed by the EORTC-PR25 (p>0.05).ConclusionsA short-term programme of supervised exercise does not appear to enhance indices of sexual health and function in men with advanced prostate cancer. Limitations of the intervention included the conservative modular exercise programme, which deliberately avoided loading bone metastatic sites.Trial registration numberACTRN12611001158954

    Cosmesis and breast-related quality of life outcomes following intra-operative radiotherapy for early breast cancer - a sub-study of the TARGIT - a trial

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    Purpose: The international randomized TARGIT-A trial compared risk-adapted single-dose intra-operative radiotherapy (TARGIT-IORT) to 3-7 weeks of daily conventional external beam radiotherapy (EBRT) in women with early breast cancer treatable with breast conserving surgery. TARGIT-A showed TARGIT-IORT to be non-inferior compared to EBRT in terms of reducing the risk of local cancer recurrence and found no difference in breast cancer survival however its effect on patient reported cosmesis and breast-related quality of life (QOL) have not yet been described. Methods and Materials: Longitudinal cosmesis and QOL data were collected from a sub-set of TARGIT-A participants who received TARGIT-IORT as a separate procedure (post-pathology). Patients completed a cosmetic assessment before radiotherapy and annually thereafter for at least five years. Patients also completed the combined EORTC core questionnaire (QLQ-C30) and Breast Specific Module (BR23) in addition to the Body Image after Breast Cancer Questionnaire (BIABC) at baseline and annually thereafter. The combined EORTC questionnaires were also collected 3, 6, and 9 months after wide local excision (WLE). Results: An Excellent-Good (EG) cosmetic result was scored more often than a Fair-Poor (FP) result for both treatment groups across all time points. TARGIT-IORT patients reported better breast-related QOL than EBRT patients. Statistically and clinically significant differences were seen at month-6 and Year-1, with EBRT patients having moderately worse breast symptoms (a statistically significant difference of more than 10 in a 100 point scale) than TARGIT-IORT patients at these time points. Conclusion: Patients treated with TARGIT-IORT on the TARGIT-A trial have similar self-reported cosmetic outcome but better breast-related QOL outcomes than patients treated with EBRT. This important evidence can facilitate the treatment decision making process for patients who have early breast cancer suitable for breast conserving surgery and inform their clinicians

    Bridging the Communications Gap between Systems and Software Engineering 1

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    Abstract. Kasser and Shoshany (2000) identified that differences in communications between systems and software engineers were a cause of project failure 2 . This paper introduces a methodology for use by integrated process teams (IPT) to bridge the communications gap between systems and software engineering. The meta-model for the development process (Kasser and Shoshany 2000) shows that engineers use pattern matching techniques. However, systems and software engineers tend to use different patterns. This paper shows that the sharing of patterns may bridge the communications gap. For it is by sharing of mental patterns that the engineers can understand and communicate the impact of a concept on their discipline. The paper also provides some examples of how patterns may be shared in an integrated design team environment

    Effectiveness and cost-effectiveness of a multidisciplinary intervention programme to prevent new falls and functional decline among elderly persons at risk: design of a replicated randomised controlled trial [ISRCTN64716113]

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    BACKGROUND: Falls are common among community-dwelling elderly people and can have a considerable impact on quality of life and healthcare costs. People who have sustained a fall are at greater risk of falling again. We replicated a British randomised controlled trial which demonstrated the effectiveness of a multidisciplinary intervention programme to prevent falls. The objective is to describe the design of a replication study evaluating a multidisciplinary intervention programme on recurrent falls and functional decline among elderly persons at risk. The study consists of an effect evaluation, an economic evaluation and a process evaluation. METHODS/DESIGN: The programme is aimed at community-dwelling elderly people aged 65 years or over who have visited an accident and emergency department (A&E department) or a general practitioners' cooperative (GP cooperative) because of a fall. The design involves a two-group randomised controlled trial. Participants are followed for twelve months after baseline. The intervention programme consists of a detailed medical and occupational therapy assessment with referral to relevant services if indicated. People in the control group receive usual care. The main outcome measures of the effect evaluation are number of falls and daily functioning. The economic evaluation will be performed from a societal perspective. A process evaluation will be carried out to evaluate the feasibility of the intervention programme

    Relationship between location and activity in injurious falls: an exploratory study

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    <p>Abstract</p> <p>Background</p> <p>Knowledge about the circumstances under which injurious falls occur could provide healthcare workers with better tools to prevent falls and fall-related injuries. Therefore, we assessed whether older persons who sustain an injurious fall can be classified into specific fall types, based on a combination of fall location and activity up to the moment of the fall. In addition, we assessed whether specific injurious fall types are related to causes of the fall, consequences of the fall, socio-demographic characteristics, and health-related characteristics.</p> <p>Methods</p> <p>An exploratory, cross-sectional study design was used to identify injurious fall types. The study population comprised 333 community-dwelling Dutch elderly people aged 65 years or over who attended an accident and emergency department after a fall. All participants received a self-administered questionnaire after being discharged home. The questionnaire comprised items concerning circumstances of the injurious fall, causes of the fall, consequences of the fall, socio-demographic characteristics and health-related characteristics. Injurious fall types were distinguished by analyzing data by means of HOMALS (homogeneity analysis by means of alternating least squares).</p> <p>Results</p> <p>We identified 4 injurious fall types: 1) Indoor falls related to lavatory visits (hall and bathroom); 2) Indoor falls during other activities of daily living; 3) Outdoor falls near the home during instrumental activities of daily living; 4) Outdoor falls away from home, occurring during walking, cycling, and shopping for groceries. These injurious fall types were significantly related to age, cause of the fall, activity avoidance and daily functioning.</p> <p>Conclusion</p> <p>The face validity of the injurious fall typology is obvious. However, we found no relationship between the injurious fall types and severity of the consequences of the fall. Nevertheless, there appears to be a difference between the prevalence of fractures and the cause of the fall between the injurious fall types. Our data suggests that with regard to prevention of serious injuries, we should pay special attention to outdoor fallers and indoor fallers during lavatory visits. In addition, we should have special attention for causes of the fall. However, the conclusions reached in this exploratory analysis are tentative and need to be validated in a separate dataset.</p

    A comparison of random forests, boosting and support vector machines for genomic selection

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    Genomic selection (GS) involves estimating breeding values using molecular markers spanning the entire genome. Accurate prediction of genomic breeding values (GEBVs) presents a central challenge to contemporary plant and animal breeders. The existence of a wide array of marker-based approaches for predicting breeding values makes it essential to evaluate and compare their relative predictive performances to identify approaches able to accurately predict breeding values. We evaluated the predictive accuracy of random forests (RF), stochastic gradient boosting (boosting) and support vector machines (SVMs) for predicting genomic breeding values using dense SNP markers and explored the utility of RF for ranking the predictive importance of markers for pre-screening markers or discovering chromosomal locations of QTLs
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