Modern sediment records of hydroclimatic extremes and associated potential contaminant mobilization in semi-arid environments : lessons learnt from recent flood-drought cycles in southern Botswana

Open access via the Springer Compact Agreement This research was funded by the UK Natural Environment Research Council NERC Urgency grant NE/R002568/1 (PULA Project). Acknowledgments The authors would like to thank the Editor and two anonymous reviewers for their comments and suggestions which have contributed to improve the quality of this paper. The authors would like to thank all the BIUST students that took part in one or more field campaigns in the Notwane river catchment; their work and interests were remarkable. Thanks are due to Trust Manyiwa (BIUST) for the assistance with grain size and OM analyses and to Serwalo M. Mokgosi (BIUST) for assistance with the MP-AES measurements of sediment materials. We would like to thank the staff at the University of Aberdeen laboratory (Michael McGibbon) for assistance with the water quality analyses.Peer reviewedPublisher PD

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

Surface water-groundwater interactions and local land use control water quality impacts of extreme rainfall and flooding in a vulnerable semi-arid region of Sub-Saharan Africa

Acknowledgements This work was funded by the UK Natural Environment Research Council (grant references NE/R002568/1 and NE/S005943/1). We would like to thank Gaone Johwa, Olerilwe Masisi, Lillian Molose and Mosireletsi Rakolanyana (BIUST) and Botswana Department of Water Affairs staff for assistance with field data collection campaigns. Thanks are due to Gizaw Mengistu Tsidu (BIUST) for the assistance with obtaining the CHIRP data set. The Botswana Department of Water Affairs is also thanked for the provision of borehole level data. Michael McGibbon, David Galloway and Audrey Innes are thanked for laboratory assistance with water quality and stable water isotope analyses. We would also like to thank the wider team at the Botswana Department of Water Affairs and local community chiefs for useful discussions.Peer reviewedPublisher PD