Effects of arterial cannulation stress on regional cerebral blood flow in major depressive disorder

Individuals with major depressive disorder (MDD) display abnormal neurophysiological responses to psychological stress but little is known about their neurophysiological responses to physiological stressors. Using [15O-H2O] positron emission tomography we assessed whether the regional cerebral blood flow (rCBF) response to arterial cannulation differed between patients with MDD and healthy controls (HCs). Fifty-one MDD patients and 62 HCs were scanned following arterial cannulation and 15 MDD patients and 17 HCs were scanned without arterial cannulation. A region-of-interest analysis showed that a significantly increased rCBF of the anterior cingulate cortex and right amygdala was associated with arterial cannulation in MDD. A whole brain analysis showed increased rCBF of the right post-central gyrus, left temporopolar cortex, and right amygdala during arterial cannulation in MDD patients. The rCBF in the right amygdala was significantly correlated with depression severity. Conceivably, the limbic response to invasive physical stress is greater in MDD subjects than in HCs

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

Effects of arterial cannulation stress on regional cerebral blood flow in major depressive disorder

Individuals with major depressive disorder (MDD) display abnormal neurophysiological responses to psychological stress but little is known about their neurophysiological responses to physiological stressors. Using [O-15]-H2O positron emission tomography we assessed whether the regional cerebral blood flow (rCBF) response to arterial cannulation differed between patients with MDD and healthy controls (HCs). Fifty-one MDDpatients and 62 HCs were scanned following arterial cannulation and 15MDDpatients and 17 HCs were scanned without arterial cannulation. A region-of-interest analysis showed that a significantly increased rCBF of the anterior cingulate cortex and right amygdala was associated with arterial cannulation in MDD. A whole brain analysis showed increased rCBF of the right post-central gyrus, left temporopolar cortex, and right amygdala during arterial cannulation in MDD patients. The rCBF in the right amygdala was significantly correlated with depression severity. Conceivably, the limbic response to invasive physical stress is greater in MDD subjects than in HCs

Reviews and syntheses: The promise of big soil data, moving current practices towards future potential

In the age of big data, soil data are more available than ever, but -outside of a few large soil survey resources- remain largely unusable for informing soil management and understanding Earth system processes outside of the original study. Data science has promised a fully reusable research pipeline where data from past studies are used to contextualize new findings and reanalyzed for global relevance. Yet synthesis projects encounter challenges at all steps of the data reuse pipeline, including unavailable data, labor-intensive transcription of datasets, incomplete metadata, and a lack of communication between collaborators. Here, using insights from a diversity of soil, data and climate scientists, we summarize current practices in soil data synthesis across all stages of database creation: data discovery, input, harmonization, curation, and publication. We then suggest new soil-focused semantic tools to improve existing data pipelines, such as ontologies, vocabulary lists, and community practices. Our goal is to provide the soil data community with an overview of current practices in soil data and where we need to go to fully leverage big data to solve soil problems in the next century.ISSN:1810-6277ISSN:1810-628

Now He Belongs to the Ages”: The Heroic Leadership Dynamic and Deep Narratives of Greatness

In this article, we review the psychology of hero development and hero worship. Heroes and hero narratives fulfill important cognitive and emotional needs, including the need for wisdom, meaning, hope, inspiration, and growth. Hero stories provide epistemic benefits by providing scripts for prosocial action, by revealing fundamental truths about human existence, by unpacking life paradoxes, and by cultivating emotional intelligence. To energize us, heroes promote moral elevation, heal psychic wounds, inspire psychological growth, and exude charisma