14,194 research outputs found

    Operators' Accessibility Studies using Virtual Reality

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    International audienceThe development of fusion plants is more and more challenging. Compared to previous fusion experimental devices, integration constraints, maintenance and safety requirements are key parameters in the ITER project. Components are designed in parallel and we must consider integration, assembly and maintenance issues, which might have a huge impact on the overall design. That also implies to consider the operator's feedback to assess the feasibility of accessibility or maintenance processes. Virtual reality (VR) provides tools to optimize such integration. In 2010, the CEA IRFM decided to upgrade its design tools, by using VR during the life cycle (from design to operation) of a fusion component. The VR platform is intensively used in the design and assembly studies of WEST components. In particular, feasibility of the assembly scenario is assessed by the operators involving in the real assembly work. To study this aspect, the use of static manikins is quite frequent in the industry. However, more complex studies, like the feasibility of assembly and maintenance tasks in complex and very confined environments, require enhanced features such as dynamic and biomechanically realistic virtual humans. We also study the contribution of tactile feedback to improve physical presence and interaction in the virtual environment (VE), which is very important for the validation of a given task's feasibility and the ergonomic evaluation of the posture and gesture of the operator. In particular, we show that adapted behavior in respect to physical elements of the VE can be obtained using a dynamic co-localized representation of the subject's body and a pseudo-haptic tactile feedback. In this paper, we present integration studies involving operators and recent advances in the assessment of maintenance feasibility

    The effect of PD-L1 testing on the cost-effectiveness and economic impact of immune checkpoint inhibitors for the second-line treatment of NSCLC

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    Background: Immune checkpoint inhibitors improve outcomes compared with chemotherapy in lung cancer. Tumor PD-L1 receptor expression is being studied as a predictive biomarker. The objective of this study was to assess the cost-effectiveness and economic impact of second-line treatment with nivolumab, pembrolizumab, and atezolizumab with and without the use of PD-L1 testing for patient selection. Design: We developed a decision-analytic model to determine the cost-effectiveness of PD-L1 assessment and second-line immunotherapy versus docetaxel. The model used outcomes data from randomized clinical trials (RCTs) and drug acquisition costs from the United States. Thereafter, we used epidemiologic data to estimate the economic impact of the treatment. Results: We included four RCTs (2 with nivolumab, 1 with pembrolizumab, and 1 with atezolizumab). The incremental quality-adjusted life year (QALY) for nivolumab was 0.417 among squamous tumors and 0.287 among non-squamous tumors and the incremental cost-effectiveness ratio (ICER) were 155605and155 605 and 187 685, respectively. The QALY gain in the base case for atezolizumab was 0.354 and the ICER was 215802.Comparedwithtreatingallpatients,theselectionofpatientsbyPD−L1expressionimprovedincrementalQALYbyupto183215 802. Compared with treating all patients, the selection of patients by PD-L1 expression improved incremental QALY by up to 183% and decreased the ICER by up to 65%. Pembrolizumab was studied only in patients whose tumors expressed PD-L1. The QALY gain was 0.346 and the ICER was 98 421. Patient selection also reduced the budget impact of immunotherapy. Conclusion: The use of PD-L1 expression as a biomarker increases cost-effectiveness of immunotherapy but also diminishes the number of potential life-years saved.info:eu-repo/semantics/publishedVersio

    Building capacity for clinical research in developing countries: the INDOX cancer research network experience

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    Transnational Organisations increasingly prioritise the need to support local research capacity in low and middle income countries in order that local priorities are addressed with due consideration of contextual issues. There remains limited evidence on the best way in which this should be done or the ways in which external agencies can support this process

    Identification of a Proliferation Gene Cluster Associated with HPV E6/E7 Expression Level and Viral DNA Load in Invasive Cervical Carcinoma

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    Specific HPV DNA sequences are associated with more than 90% of invasive carcinomas of the uterine cervix. Viral E6 and E7 oncogenes are key mediators in cell transformation by disrupting TP53 and RB pathways. To investigate molecular mechanisms involved in the progression of invasive cervical carcinoma, we performed a gene expression study on cases selected according to viral and clinical parameters. Using Coupled Two-Way Clustering and Sorting Points Into Neighbourhoods methods, we identified a Cervical Cancer Proliferation Cluster composed of 163 highly correlated transcripts, many of which corresponded to E2F pathway genes controlling cell proliferation, whereas no primary TP53 targets were present in this cluster. The average expression level of the genes of this cluster was higher in tumours with an early relapse than in tumours with a favourable course (P=0.026). Moreover, we found that E6/E7 mRNA expression level was positively correlated with the expression level of the cluster genes and with viral DNA load. These findings suggest that HPV E6/E7 expression level plays a key role in the progression of invasive carcinoma of the uterine cervix via the deregulation of cellular genes controlling tumour cell proliferation. HPV expression level may thus correspond to a biological marker useful for prognosis assessment and specific therapy of the disease

    Global burden of cancers attributable to infections in 2012:a synthetic analysis

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    Background Infections with certain viruses, bacteria, and parasites are strong risk factors for specifi c cancers. As new cancer statistics and epidemiological fi ndings have accumulated in the past 5 years, we aimed to assess the causal involvement of the main carcinogenic agents in diff erent cancer types for the year 2012. Methods We considered ten infectious agents classifi ed as carcinogenic to human beings by the International Agency for Research on Cancer. We calculated the number of new cancer cases in 2012 attributable to infections by country, by combining cancer incidence estimates (from GLOBOCAN 2012) with estimates of attributable fraction (AF) for the infectious agents. AF estimates were calculated from the prevalence of infection in cancer cases and the relative risk for the infection (for some sites). Estimates of infection prevalence, relative risk, and corresponding 95% CIs for AF were obtained from systematic reviews and pooled analyses. Findings Of 14 million new cancer cases in 2012, 2·2 million (15·4%) were attributable to carcinogenic infections. The most important infectious agents worldwide were Helicobacter pylori (770 000 cases), human papillomavirus (640 000), hepatitis B virus (420 000), hepatitis C virus (170 000), and Epstein-Barr virus (120 000). Kaposi’s sarcoma was the second largest contributor to the cancer burden in sub-Saharan Africa. The AFs for infection varied by country and development status—from less than 5% in the USA, Canada, Australia, New Zealand, and some countries in western and northern Europe to more than 50% in some countries in sub-Saharan Africa. Interpretation A large potential exists for reducing the burden of cancer caused by infections. Socioeconomic development is associated with a decrease in infection-associated cancers; however, to reduce the incidence of these cancers without delay, population-based vaccination and screen-and-treat programmes should be made accessible and available
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