266 research outputs found

    Efficient and Robust NK-Cell Transduction With Baboon Envelope Pseudotyped Lentivector

    Get PDF
    NK-cell resistance to transduction is a major technical hurdle for developing NK-cell immunotherapy. By using Baboon envelope pseudotyped lentiviral vectors (BaEV-LVs) encoding eGFP, we obtained a transduction rate of 23.0 ± 6.6% (mean ± SD) in freshly-isolated human NK-cells (FI-NK) and 83.4 ± 10.1% (mean ± SD) in NK-cells obtained from the NK-cell Activation and Expansion System (NKAES), with a sustained transgene expression for at least 21 days. BaEV-LVs outperformed Vesicular Stomatitis Virus type-G (VSV-G)-, RD114- and Measles Virus (MV)- pseudotyped LVs (p < 0.0001). mRNA expression of both BaEV receptors, ASCT1 and ASCT2, was detected in FI-NK and NKAES, with higher expression in NKAES. Transduction with BaEV-LVs encoding for CAR-CD22 resulted in robust CAR-expression on 38.3 ± 23.8% (mean ± SD) of NKAES cells, leading to specific killing of NK-resistant pre-B-ALL-RS4;11 cell line. Using a larger vector encoding a dual CD19/CD22-CAR, we were able to transduce and re-expand dual-CAR-expressing NKAES, even with lower viral titer. These dual-CAR-NK efficiently killed both CD19KO- and CD22KO-RS4;11 cells. Our results suggest that BaEV-LVs may efficiently enable NK-cell biological studies and translation of NK-cell-based immunotherapy to the clinic

    Terrestrial laser scanning for plot-scale forest measurement

    Get PDF
    Plot-scale measurements have been the foundation for forest surveys and reporting for over 200 years. Through recent integration with airborne and satellite remote sensing, manual measurements of vegetation structure at the plot scale are now the basis for landscape, continental and international mapping of our forest resources. The use of terrestrial laser scanning (TLS) for plot-scale measurement was first demonstrated over a decade ago, with the intimation that these instruments could replace manual measurement methods. This has not yet been the case, despite the unparalleled structural information that TLS can capture. For TLS to reach its full potential, these instruments cannot be viewed as a logical progression of existing plot-based measurement. TLS must be viewed as a disruptive technology that requires a rethink of vegetation surveys and their application across a wide range of disciplines. We review the development of TLS as a plotscale measurement tool, including the evolution of both instrument hardware and key data processing methodologies. We highlight two broad data modelling approaches of gap probability and geometrical modelling and the basic theory that underpins these. Finally, we discuss the future prospects for increasing the utilisation of TLS for plot-scale forest assessment and forest monitoring

    A multidisciplinary systematic literature review on frailty: Overview of the methodology used by the Canadian Initiative on Frailty and Aging

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Over the past two decades, there has been a substantial growth in the body of literature on frailty in older persons. However, there is no consensus on its definition or the criteria used to identify frailty. In response to this lack of consensus, the Canadian Initiative on Frailty and Aging carried out a set of systematic reviews of the literature in ten areas of frailty research: biological basis; social basis; prevalence; risk factors; impact; identification; prevention and management; environment and technology; health services; health and social policy. This paper describes the methodology that was developed for the systematic reviews.</p> <p>Methods</p> <p>A Central Coordination Group (CCG) was responsible for developing the methodology. This involved the development of search strategies and keywords, article selection processes, quality assessment tools, and guidelines for the synthesis of results. Each review was conducted by two experts in the content area, with the assistance of methodologists and statisticians from the CCG.</p> <p>Results</p> <p>Conducting a series of systematic literature reviews involving a range of disciplines on a concept that does not have a universally accepted definition posed several conceptual and methodological challenges. The most important conceptual challenge was determining what would qualify as literature on frailty. The methodological challenges arose from our goal of structuring a consistent methodology for reviewing literature from diverse fields of research. At the outset, certain methodological guidelines were deemed essential to ensure the validity of all the reviews. Nevertheless, it was equally important to permit flexibility in the application of the proposed methodology to capture the essence of frailty research within the given fields.</p> <p>Conclusion</p> <p>The results of these reviews allowed us to establish the status of current knowledge on frailty and promote collaboration between disciplines. Conducting systematic literature reviews in health science that involve multiple disciplines is a mechanism to facilitate interdisciplinary collaboration and a more integrated understanding of health. This initiative highlighted the need for further methodological development in the performance of multidisciplinary systematic reviews.</p

    An Earth-system prediction initiative for the twenty-first century

    Get PDF
    International audienceSome scientists have proposed the Earth-System Prediction Initiative (EPI) at the 2007 GEO Summit in Cape Town, South Africa. EPI will draw upon coordination between international programs for Earth system observations, prediction, and warning, such as the WCRP, WWRP, GCOS, and hence contribute to GEO and the GEOSS. It will link with international organizations, such as the International Council for Science (ICSU), Intergovernmental Oceanographic Commission (IOC), UNEP, WMO, and World Health Organization (WHO). The proposed initiative will provide high-resolution climate models that capture the properties of regional high-impact weather events, such as tropical cyclones, heat wave, and sand and dust storms associated within multi-decadal climate projections of climate variability and change. Unprecedented international collaboration and goodwill are necessary for the success of EPI

    Longevity and relationships with children: the importance of the parental role

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Social networks predict longevity across societies but specific mechanisms are largely unknown. The aim of this work was to examine the role of children in the longevity of elderly men and women in a cohort of community dwelling elderly people in Spain.</p> <p>Methods</p> <p>The data were taken from the "Aging in Leganes" cohort study with 15 years of follow-up. The baseline population was an age- and sex-stratified random sample of community dwelling people over 65 living in Leganés (Madrid) in 1993. Poor relationship with at least one child, emotional support and the perceived roles elders play in the lives of their children, extended family, spouse and friends were assessed at baseline. Cox proportional hazards models were fit to investigate the effects of social roles variables on longevity, adjusting for a wide range of socioeconomic, behavioural and health covariates.</p> <p>Results</p> <p>In the fully adjusted model, having a poor relationship with at least one child increased mortality by 30%. Elderly persons who felt their role in their children's lives was important (HR = 0.70; 95% CI 0.54; 0.91) had a lower mortality risk than those who felt they played a small role. Feeling loved and listened to by one's children did not have an effect on survival. Maintaining an important role in the extended family was also significantly associated with survival.</p> <p>Conclusion</p> <p>In this Mediterranean population, maintaining an important role in the lives of one's children is associated with survival. Functions of social networks related to meaning of life and different forms of social support may have important effects on mortality, and these functions may vary across cultures according to family norms and values.</p
    corecore