Background: Programmed death-ligand 1 (PD-L1) is upregulated in glioblastoma and supports immunosuppression. We evaluated PD-L1 blockade with durvalumab among glioblastoma cohorts and investigated potential biomarkers. Methods: MGMT unmethylated newly diagnosed patients received radiotherapy plus durvalumab (cohort A; n=40). Bevacizumab-naïve, recurrent patients received durvalumab alone (cohort B; n=31), or in combination with standard bevacizumab (cohort B2; n=33), or low-dose bevacizumab (cohort B3; n=33). Bevacizumab-refractory patients received durvalumab plus bevacizumab (cohort C; n=22). Primary endpoints were: OS-12 (A); PFS-6 (B, B2, B3); and OS-6 (C). Exploratory biomarkers included: a systematic, quantitative and phenotypic evaluation of circulating immune cells; tumor mutational burden (TMB); and tumor immune activation signature (IAS). Results: No cohort achieved the primary efficacy endpoint. Outcome was comparable among recurrent, bevacizumab-naive cohorts. No unexpected toxicities were observed. A widespread reduction of effector immune cell subsets was noted among recurrent patients compared to newly diagnosed that was partially due to dexamethasone use. A trend of increased CD8+Ki67+ T cells at day 15 was noted among patients who achieved the primary endpoint and were not on dexamethasone. Neither TMB nor IAS predicted outcome. Conclusion: Recurrent glioblastoma patients have markedly lower baseline levels of multiple circulating immune cell subsets compared to newly diagnosed patients. An early increase in systemic Ki67+CD8+ cells may warrant further evaluation as a potential biomarker of therapeutic benefit among glioblastoma patients undergoing checkpoint therapy. Dexamethasone decreased immune cell subsets. PD-L1 blockade and combination with standard or reduced dose bevacizumab was ineffective.

Compared with snack skipping, coconut oil and oat puree snacks suppressed short-term food intake, which was likely due to the sustained release of FFA and slowly digestible oats, respectively. Our in vitro digestion model predicted the relative differences in the glycemic response in vivo.

Adults’ gestures support children's learning in problem-solving tasks, but gestures may be differentially useful to children of different ages, and different features of gestures may make them more or less useful to children. The current study investigated parents’ use of gestures to support their young children (1.5 – 6 years) in a block puzzle task (N = 126 parent-child dyads), and identified patterns in parents’ gesture use indicating different gestural strategies. Further, we examined the effect of child age on both the frequency and types of gestures parents used, and on their usefulness to support children's learning. Children attempted to solve the puzzle independently before and after receiving help from their parent; half of the parents were instructed to sit on their hands while they helped. Parents who could use their hands appear to use gestures in three strategies: orienting the child to the task, providing abstract information, and providing embodied information; further, they adapted their gesturing to their child's age and skill level. Younger children elicited more frequent and more proximal gestures from parents. Despite the greater use of gestures with younger children, it was the oldest group (4.5-6.0 years) who were most affected by parents’ gestures. The oldest group was positively affected by the total frequency of parents’ gestures, and in particular, parents’ use of embodying gestures (indexes that touched their referents, representational demonstrations with object in hand, and physically guiding child's hands). Though parents rarely used the embodying strategy with older children, it was this strategy which most enhanced the problem-solving of children 4.5 – 6 years.

Sixty-two daughters provided narratives of their births and completed measures of self-esteem and motherdaughter attachment. Thirty-three of their mothers provided independent accounts of the births. Daughters who had heard the stories of their births more times wrote more descriptive and positive accounts and showed higher selfesteem and stronger attachment to their mothers than daughters who had heard the stories less often. Positivity of the mothers' narratives was correlated with daughters' self-esteem while descriptiveness of the mothers' narratives was correlated with daughters' levels of mother-daughter attachment. Raters blind to the identity of mothers and daughters made more successful matches between mothers' and daughters' stories for daughters with higher self-esteem and attachment.Keywords Birth stories . Narrative identity . Self-esteem . Mother-daughter attachment At the core of identity formation are the narrative memories that we recall from our lives (McAdams, 2001;Singer, 2004). We tell these narratives about ourselves in order to express and define who we are (Nelson, 2003). Not only do narrative memories provide a medium for self-expression and identity formation, but they also offer a way to make sense of the events in our lives. A narrative's structure can provide order, coherence, and meaning to life experiences