13 research outputs found

    Recovering the second moment of the strain distribution from neutron Bragg edge data

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    Point by point strain scanning is often used to map the residual stress (strain) in engineering materials and components. However, the gauge volume and hence spatial resolution is limited by the beam defining apertures and can be anisotropic for very low and high diffraction (scattering) angles. Alternatively, wavelength resolved neutron transmission imaging has a potential to retrieve information tomographically about residual strain induced within materials through measurement in transmission of Bragg edges - crystallographic fingerprints whose locations and shapes depend on microstructure and strain distribution. In such a case the spatial resolution is determined by the geometrical blurring of the measurement setup and the detector point spread function. Mathematically, reconstruction of strain tensor field is described by the longitudinal ray transform; this transform has a non-trivial null-space, making direct inversion impossible. A combination of the longitudinal ray transform with physical constraints was used to reconstruct strain tensor fields in convex objects. To relax physical constraints and generalise reconstruction, a recently introduced concept of histogram tomography can be employed. Histogram tomography relies on our ability to resolve the distribution of strain in the beam direction, as we discuss in the paper. More specifically, Bragg edge strain tomography requires extraction of the second moment (variance about zero) of the strain distribution which has not yet been demonstrated in practice. In this paper we verify experimentally that the second moment can be reliably measured for a previously well characterised aluminium ring and plug sample. We compare experimental measurements against numerical calculation and further support our conclusions by rigorous uncertainty quantification of the estimated mean and variance of the strain distribution

    31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

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    Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

    Comparison of three bioelectrical impedance methods with DXA in overweight and obese men

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    ObjectiveTo compare bioelectrical impedance analysis (BIA) of body composition using three different methods against DXA in overweight and obese men.Research methods and proceduresForty-three healthy overweight or obese men (ages 25 to 60 years; BMI, 28 to 43 kg/m(2)) underwent BIA assessment of body composition using the ImpediMed SFB7 (version 6; ImpediMed, Ltd., Eight Mile Plains, Queensland, Australia) in multifrequency mode (Imp-MF) and DF50 single-frequency mode (Imp-SF) and the Tanita UltimateScale (Tanita Corp., Tokyo, Japan). Validity was assessed by comparison against DXA using linear regression and limits of agreement analysis.ResultsAll three BIA methods showed good relative agreement with DXA [Imp-MF: fat mass (FM), r(2) = 0.81; fat-free mass (FFM), r(2) = 0.81; percentage body fat (BF%), r(2) = 0.69; Imp-SF: FM, r(2) = 0.65; FFM, r(2) = 0.76; BF%, r(2) = 0.40; Tanita: BF%, r(2) = 0.44; all p DiscussionCompared with DXA, Imp-MF produced large bias and wide limits of agreement, and its accuracy estimating body composition in overweight or obese men was poor. Imp-SF and Tanita demonstrated little bias and may be useful for group comparisons, but their utility for assessment of body composition in individuals is limited.Ian R. Pateyjohns, Grant D. Brinkworth, Jonathan D. Buckley, Manny Noakes and Peter M. Clifto

    sj-docx-1-eqs-10.1177_87552930231223995 – Supplemental material for The 2023 US National Seismic Hazard Model: Ground-motion characterization for the conterminous United States

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    Supplemental material, sj-docx-1-eqs-10.1177_87552930231223995 for The 2023 US National Seismic Hazard Model: Ground-motion characterization for the conterminous United States by Morgan P Moschetti, Brad T Aagaard, Sean K Ahdi, Jason Altekruse, Oliver S Boyd, Arthur D Frankel, Julie Herrick, Mark D Petersen, Peter M Powers, Sanaz Rezaeian, Allison M Shumway, James A Smith, William J Stephenson, Eric M Thompson and Kyle B Withers in Earthquake Spectra</p

    Vaccine effectiveness of primary series and booster doses against covid-19 associated hospital admissions in the United States: living test negative design study

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    AbstractObjectiveTo compare the effectiveness of a primary covid-19 vaccine series plus booster doses with a primary series alone for the prevention of hospital admission with omicron related covid-19 in the United States.DesignMulticenter observational case-control study with a test negative design.SettingHospitals in 18 US states.Participants4760 adults admitted to one of 21 hospitals with acute respiratory symptoms between 26 December 2021 and 30 June 2022, a period when the omicron variant was dominant. Participants included 2385 (50.1%) patients with laboratory confirmed covid-19 (cases) and 2375 (49.9%) patients who tested negative for SARS-CoV-2 (controls).Main outcome measuresThe main outcome was vaccine effectiveness against hospital admission with covid-19 for a primary series plus booster doses and a primary series alone by comparing the odds of being vaccinated with each of these regimens versus being unvaccinated among cases versus controls. Vaccine effectiveness analyses were stratified by immunosuppression status (immunocompetent, immunocompromised). The primary analysis evaluated all covid-19 vaccine types combined, and secondary analyses evaluated specific vaccine products.ResultsOverall, median age of participants was 64 years (interquartile range 52-75 years), 994 (20.8%) were immunocompromised, 85 (1.8%) were vaccinated with a primary series plus two boosters, 1367 (28.7%) with a primary series plus one booster, and 1875 (39.3%) with a primary series alone, and 1433 (30.1%) were unvaccinated. Among immunocompetent participants, vaccine effectiveness for prevention of hospital admission with omicron related covid-19 for a primary series plus two boosters was 63% (95% confidence interval 37% to 78%), a primary series plus one booster was 65% (58% to 71%), and for a primary series alone was 37% (25% to 47%) (P<0.001 for the pooled boosted regimens compared with a primary series alone). Vaccine effectiveness was higher for a boosted regimen than for a primary series alone for both mRNA vaccines (BNT162b2 (Pfizer-BioNTech): 73% (44% to 87%) for primary series plus two boosters, 64% (55% to 72%) for primary series plus one booster, and 36% (21% to 48%) for primary series alone (P<0.001); mRNA-1273 (Moderna): 68% (17% to 88%) for primary series plus two boosters, 65% (55% to 73%) for primary series plus one booster, and 41% (25% to 54%) for primary series alone (P=0.001)). Among immunocompromised patients, vaccine effectiveness for a primary series plus one booster was 69% (31% to 86%) and for a primary series alone was 49% (30% to 63%) (P=0.04).ConclusionDuring the first six months of 2022 in the US, booster doses of a covid-19 vaccine provided additional benefit beyond a primary vaccine series alone for preventing hospital admissions with omicron related covid-19.Readers’ noteThis article is a living test negative design study that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication
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