150 research outputs found

    Infrared Behaviour of SU(2) Gauge Theory with Nf fundamental flavours

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    We review our recent results on the infrared behaviour of the SU(2) gauge theory with Nf massless fundamental flavour fermions. We have analyzed the running of the coupling in SU(2) gauge theories with six and eight fermionic flavours using the gradient flow step scaling method. From the running of the coupling, we see a clear indication of an infrared stable fixed point in theories with six and eight flavours. These results are confirmed by our mass spectrum study, where we varied the number of flavours from two to six. We also compute the anomalous dimensions of mass and coupling.Peer reviewe

    TNFa and IL-2 armed adenoviruses enable complete responses by anti-PD-1 checkpoint blockade

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    Releasing the patient's immune system against their own malignancy by the use of checkpoint inhibitors is delivering promising results. However, only a subset of patients currently benefit from them. One major limitation of these therapies relates to the inability of T cells to detect or penetrate into the tumor resulting in unresponsiveness to checkpoint inhibition. Virotherapy is an attractive tool for enabling checkpoint inhibitors as viruses are naturally recognized by innate defense elements which draws the attention of the immune system. Besides their intrinsic immune stimulating properties, the adenoviruses used here are armed to express tumor necrosis factor alpha (TNFa) and interleukin-2 (IL-2). These cytokines result in immunological danger signaling and multiple appealing T-cell effects, including trafficking, activation and propagation. When these viruses were injected into B16.OVA melanoma tumors in animals concomitantly receiving programmed cell-death protein 1 (PD-1) blocking antibodies both tumor growth control (p <0.0001) and overall survival (p <0.01) were improved. In this set-up, the addition of adoptive cell therapy with OT-I lymphocytes did not increase efficacy further. When virus injections were initiated before antibody treatment in a prime-boost approach, 100% of tumors regressed completely and all mice survived. Viral expression of IL2 and TNFa altered the cytokine balance in the tumor microenvironment towards Th1 and increased the intratumoral proportion of CD8+ and conventional CD4+ T cells. These preclinical studies provide the rationale and schedule for a clinical trial where oncolytic adenovirus coding for TNFa and IL-2 (TILT-123) is used in melanoma patients receiving an anti-PD-1 antibody.Peer reviewe

    Adaptation of pain scales for parent observation: are pain scales and symptoms useful in detecting pain of young children with the suspicion of acute otitis media?

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    BackgroundThe assessment of ear pain is challenging in young, mostly preverbal children. Our aim was to investigate whether pain scales are useful tools for parents to detect pain in their young children with the suspicion of acute otitis media (AOM), and to assess associations between 16 symptoms and the severity of pain.MethodsThis cross-sectional study included 426 children (6-35months) with symptoms suggestive of AOM. We surveyed symptoms and pain via parental interview. As part of the interview, parents assessed their child's pain by using two pain scales: The Faces Pain Scale-Revised (FPS-R) and the Face, Legs, Activity, Cry, Consolability (FLACC) Scale. The outcome of interest was moderate/severe pain. We used the (2) test or Fisher's test as applicable to compare the severity of pain between three parental pain assessment methods (the parental interview, the FPS-R and the FLACC Scale). We also used multivariable logistic regression models to study the association between the severity of pain and AOM and to study the association between symptoms and the severity of pain.ResultsIn children with AOM (n=201), pain was assessed by parents as moderate/severe in 65% via interview; 90% with the FPS-R; and 91% with the FLACC Scale (P<0.001). In children without AOM (n=225), the percentages were 56, 83 and 88%, respectively (P<0.001). Between children with and without AOM, the occurrence of moderate/severe pain did not differ with any of the pain evaluation methods. Of symptoms, ear pain reported by child and restless sleep were significantly associated with moderate/severe pain, regardless of the pain evaluation method.ConclusionsIt seems that nearly all the children with respiratory tract infection, either with or without AOM, might suffer from moderate/severe pain. Without pain scales, parents may underestimate their child's pain. Of symptoms, ear pain reported by child and restless sleep might indicate pain in children with respiratory tract infection. We suggest that the adaptation of pain scales for parent observation is a possibility in children with respiratory tract infection which, however, requires further studies.Trial registrationwww.clinicaltrials.gov, identifier NCT00299455. Date of registration: March 3, 2006
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