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

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

Royal Philips Medical Technology: repositioning to MedTech

Equity research repor

Search for Higgs and ZZ Boson Decays to J/ψγJ/\psi\gamma and Υ(nS)γ\Upsilon(nS)\gamma with the ATLAS Detector

A search for the decays of the Higgs and $Z$ bosons to $J/\psi\gamma$ and $\Upsilon(nS)\gamma$ ($n=1,2,3$) is performed with $pp$ collision data samples corresponding to integrated luminosities of up to $20.3\mathrm{fb}^{-1}$ collected at $\sqrt{s}=8\mathrm{TeV}$ with the ATLAS detector at the CERN Large Hadron Collider. No significant excess of events is observed above expected backgrounds and 95% CL upper limits are placed on the branching fractions. In the $J/\psi\gamma$ final state the limits are $1.5\times10^{-3}$ and $2.6\times10^{-6}$ for the Higgs and $Z$ bosons, respectively, while in the $\Upsilon(1S,2S,3S)\,\gamma$ final states the limits are $(1.3,1.9,1.3)\times10^{-3}$ and $(3.4,6.5,5.4)\times10^{-6}$, respectively

Measurements of the Total and Differential Higgs Boson Production Cross Sections Combining the H??????? and H???ZZ*???4??? Decay Channels at s\sqrt{s}=8??????TeV with the ATLAS Detector

Measurements of the total and differential cross sections of Higgs boson production are performed using 20.3~fb$^{-1}$ of $pp$ collisions produced by the Large Hadron Collider at a center-of-mass energy of $\sqrt{s} = 8$ TeV and recorded by the ATLAS detector. Cross sections are obtained from measured $H \rightarrow \gamma \gamma$ and $H \rightarrow ZZ ^{*}\rightarrow 4\ell$ event yields, which are combined accounting for detector efficiencies, fiducial acceptances and branching fractions. Differential cross sections are reported as a function of Higgs boson transverse momentum, Higgs boson rapidity, number of jets in the event, and transverse momentum of the leading jet. The total production cross section is determined to be $\sigma_{pp \to H} = 33.0 \pm 5.3 \, ({\rm stat}) \pm 1.6 \, ({\rm sys}) \mathrm{pb}$. The measurements are compared to state-of-the-art predictions.Measurements of the total and differential cross sections of Higgs boson production are performed using 20.3  fb-1 of pp collisions produced by the Large Hadron Collider at a center-of-mass energy of s=8  TeV and recorded by the ATLAS detector. Cross sections are obtained from measured H→γγ and H→ZZ*→4ℓ event yields, which are combined accounting for detector efficiencies, fiducial acceptances, and branching fractions. Differential cross sections are reported as a function of Higgs boson transverse momentum, Higgs boson rapidity, number of jets in the event, and transverse momentum of the leading jet. The total production cross section is determined to be σpp→H=33.0±5.3 (stat)±1.6 (syst)  pb. The measurements are compared to state-of-the-art predictions.Measurements of the total and differential cross sections of Higgs boson production are performed using 20.3 fb$^{-1}$ of $pp$ collisions produced by the Large Hadron Collider at a center-of-mass energy of $\sqrt{s} = 8$ TeV and recorded by the ATLAS detector. Cross sections are obtained from measured $H \rightarrow \gamma \gamma$ and $H \rightarrow ZZ ^{*}\rightarrow 4\ell$ event yields, which are combined accounting for detector efficiencies, fiducial acceptances and branching fractions. Differential cross sections are reported as a function of Higgs boson transverse momentum, Higgs boson rapidity, number of jets in the event, and transverse momentum of the leading jet. The total production cross section is determined to be $\sigma_{pp \to H} = 33.0 \pm 5.3 \, ({\rm stat}) \pm 1.6 \, ({\rm sys}) \mathrm{pb}$. The measurements are compared to state-of-the-art predictions

Finska tingsdomares bedömningar av partsutlåtanden givna på plats i rätten eller via videokonferens

Professionals within the judicial system sometimes believe they can assess whether someone is lying or not based on cues such as body language and emotional expression. Research has, however, shown that this is impossible. The Finnish Supreme Court has also given rulings in accordance with this demonstrated fact. There has also been previous research on whether party or witness statements are assessed differently in court depending on whether they are given live, via videoconference, or via prerecorded video. In the present study, we investigated how a Finnish sample of district judges (N=47) assigned probative value to different variables concerning the statement or the statement giver, such as body language and emotional expression. We also investigated the connection between the judges’ beliefs about the relevance of body language and emotional expression and their preference for live statements or statements via videoconference. The judges reported assigning equal amounts of probative value to statements given live and statements given via videoconference. However, judges found it easier to detect deception live, and this preference correlated with how relevant they thought body language is when assessing the probative value of the statement. In other words, a slight bias to assess live statements more favorably than statements given via videoconference might still exist. More effort needs to be put into making judges and Supreme Courts aware of robust scientific results that have been the subject of decades of research, such as the fact that one cannot assess whether someone is lying or not based on cues such as body language

Search for Scalar-Charm pair production in pp collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

The results of a dedicated search for pair production of scalar partners of charm quarks are reported. The search is based on an integrated luminosity of 20.3 fb$^{-1}$ of pp collisions at $\sqrt{s}=8$ TeV recorded with the ATLAS detector at the LHC. The search is performed using events with large missing transverse momentum and at least two jets, where the two leading jets are each tagged as originating from c-quarks. Events containing isolated electrons or muons are vetoed. In an R-parity-conserving minimal supersymmetric scenario in which a single scalar-charm state is kinematically accessible, and where it decays exclusively into a charm quark and a neutralino, 95% confidence-level upper limits are obtained in the scalar-charm-neutralino mass plane such that, for neutralino masses below 200 GeV, scalar-charm masses up to 490 GeV are excluded

Search for Higgs and Z Boson Decays to J/ψγJ/\psi\gamma and Υ(nS)γ\Upsilon(nS)\gamma with the ATLAS Detector

A search for the decays of the Higgs and Z bosons to J/ψγ and ϒ(nS)γ (n=1,2,3) is performed with pp collision data samples corresponding to integrated luminosities of up to 20.3 fb-1 collected at s=8 TeV with the ATLAS detector at the CERN Large Hadron Collider. No significant excess of events is observed above expected backgrounds and 95% C.L. upper limits are placed on the branching fractions. In the J/ψγ final state the limits are 1.5×10-3 and 2.6×10-6 for the Higgs and Z boson decays, respectively, while in the ϒ(1S,2S,3S)γ final states the limits are (1.3,1.9,1.3)×10-3 and (3.4,6.5,5.4)×10-6, respectively