9 research outputs found

    ATLAS detector and physics performance: Technical Design Report, 1

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    International validation of the EORTC QLQ-ANL27, a field study to test the anal cancer-specific health-related quality of life questionnaire

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    Background: The European Organisation for Research and Treatment of Cancer (EORTC) health-related quality of life (HRQoL) questionnaire for anal cancer (QLQ-ANL27) supplements the EORTC cancer generic measure (QLQ-C30) to measure concerns specific to people with anal cancer treated with chemoradiotherapy (CRT). This study tests the psychometric properties and acceptability of the QLQ-ANL27.Materials and methods: People with anal cancer were recruited from 15 countries to complete the QLQ-C30 and QLQ-ANL27 and provide feedback on the QLQ-ANL27. Item responses, scale structure (multi-trait scaling, factor analysis), reliability (internal consistency and reproducibility) and sensitivity (known group comparisons and responsiveness to change) of the QLQ-ANL27 were evaluated.Results: Data from 382 people were included in the analyses. The EORTC QLQ-ANL27 was acceptable, comprehensive, and easy to complete, taking an average 8 minutes to complete. Psychometric analyses supported the EORTC QLQ-ANL27 items and reliability (Cronbach's alpha ranging from 0.71 to 0.93 and test-retest coefficients above 0.7) and validity of the scales (particularly non stoma bowel symptoms and pain/discomfort). Most scales distinguished people according to treatment phase and performance status. Bowel (non-stoma), pain/discomfort and vaginal symptoms were sensitive to deteriorations over time. The stoma-related scales remained untested due to low numbers of people with a stoma. Revisions to the scoring and question ordering of the sexual items were proposed.Conclusions: The QLQ-ANL27 has good psychometric properties and is available in 16 languages, for people treated with CRT for anal cancer. It is used in clinical trials and has a potential role in clinical practice.<br/

    Deconstructing Tick Saliva: NON-PROTEIN MOLECULES WITH POTENT IMMUNOMODULATORY PROPERTIES*

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    Dendritic cells (DCs) are powerful initiators of innate and adaptive immune responses. Ticks are blood-sucking ectoparasite arthropods that suppress host immunity by secreting immunomodulatory molecules in their saliva. Here, compounds present in Rhipicephalus sanguineus tick saliva with immunomodulatory effects on DC differentiation, cytokine production, and costimulatory molecule expression were identified. R. sanguineus tick saliva inhibited IL-12p40 and TNF-α while potentiating IL-10 cytokine production by bone marrow-derived DCs stimulated by Toll-like receptor-2, -4, and -9 agonists. To identify the molecules responsible for these effects, we fractionated the saliva through microcon filtration and reversed-phase HPLC and tested each fraction for DC maturation. Fractions with proven effects were analyzed by micro-HPLC tandem mass spectrometry or competition ELISA. Thus, we identified for the first time in tick saliva the purine nucleoside adenosine (concentration of ∼110 pmol/μl) as a potent anti-inflammatory salivary inhibitor of DC cytokine production. We also found prostaglandin E2 (PGE2 ∼100 nm) with comparable effects in modulating cytokine production by DCs. Both Ado and PGE2 inhibited cytokine production by inducing cAMP-PKA signaling in DCs. Additionally, both Ado and PGE2 were able to inhibit expression of CD40 in mature DCs. Finally, flow cytometry analysis revealed that PGE2, but not Ado, is the differentiation inhibitor of bone marrow-derived DCs. The presence of non-protein molecules adenosine and PGE2 in tick saliva indicates an important evolutionary mechanism used by ticks to subvert host immune cells and allow them to successfully complete their blood meal and life cycle

    ATLAS detector and physics performance: Technical Design Report, 2

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    Transport Properties

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