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

BeiDou Augmented Navigation from Low Earth Orbit Satellites

Currently, the Global Navigation Satellite System (GNSS) mainly uses the satellites in Medium Earth Orbit (MEO) to provide position, navigation, and timing (PNT) service. The weak navigation signals limit its usage in deep attenuation environments, and make it easy to interference and counterfeit by jammers or spoofers. Moreover, being far away to the Earth results in relatively slow motion of the satellites in the sky and geometric change, making long time needed for achieved centimeter positioning accuracy. By using the satellites in Lower Earth Orbit (LEO) as the navigation satellites, these disadvantages can be addressed. In this contribution, the advantages of navigation from LEO constellation has been investigated and analyzed theoretically. The space segment of global Chinese BeiDou Navigation Satellite System consisting of three GEO, three IGSO, and 24 MEO satellites has been simulated with a LEO constellation with 120 satellites in 10 orbit planes with inclination of 55 degrees in a nearly circular orbit (eccentricity about 0.000001) at an approximate altitude of 975 km. With simulated data, the performance of LEO constellation to augment the global Chinese BeiDou Navigation Satellite System (BeiDou-3) has been assessed, as one of the example to show the promising of using LEO as navigation system. The results demonstrate that the satellite visibility and position dilution of precision have been significantly improved, particularly in mid-latitude region of Asia-Pacific region, once the LEO data were combined with BeiDou-3 for navigation. Most importantly, the convergence time for Precise Point Positioning (PPP) can be shorted from about 30 min to 1 min, which is essential and promising for real-time PPP application. Considering there are a plenty of commercial LEO communication constellation with hundreds or thousands of satellites, navigation from LEO will be an economic and promising way to change the heavily relay on GNSS systems

Coupling Relationship of Urban Development and the Eco-Environment in Guanzhong Region, China

Since the 21st century, China’s rapid urban development has had profound impacts on the regional eco-environment and posed severe threats to regional sustainable development. In order to scientifically evaluate the coupling relationship between urban development and the eco-environment in the Guanzhong region, in this paper, by combining nighttime lighting data and MODIS data in 2001, 2010 and 2018, we applied an overall coupling model and a coordination model to discuss the spatial–temporal coupling and coordination relationship between urban development and the eco-environment. The results showed the following: (1) From 2001 to 2018, the urbanization development in the Guanzhong region significantly improved and the links between cities were continuously strengthened, but the degree of contact still needed to be improved. (2) The eco-environment quality in the Guanzhong region slightly increased, but the overall level was low. The structure of the eco-environment quality grade changed greatly, and “Good” grades changed to “Very Good”. (3) During 2001–2018, the overall coupling situation between urban development and the eco-environment strengthened and the degree of coordination increased. The coupling coordinator subtype gradually transformed from system balanced development into system balanced development, the ecology lag type, and the urban development lag type coexisting phenomenon. The results of the study suggest that future urban development planning and ecological protection policies need to take the coordinated coupling between urban development and the eco-environment into account

Cooling Effect of Different Land Cover Types: A Case Study in Xi’an and Xianyang, China

One of the climate problems caused by rapid urbanization is the urban heat island effect, which directly threatens the human survival environment. In general, some land cover types, such as vegetation and water, are generally considered to alleviate the urban heat island effect, because these landscapes can significantly reduce the temperature of the surrounding environment, known as the cold island effect. However, this phenomenon varies over different geographical locations, climates, and other environmental factors. Therefore, how to reasonably configure these land cover types with the cooling effect from the perspective of urban planning is a great challenge, and it is necessary to find the regularity of this effect by designing experiments in more cities. In this study, land cover (LC) classification and land surface temperature (LST) of Xi&rsquo;an, Xianyang and its surrounding areas were obtained by Landsat-8 images. The land types with cooling effect were identified and their ideal configuration was discussed through grid analysis, distance analysis, landscape index analysis and correlation analysis. The results showed that an obvious cooling effect occurred in both woodland and water at different spatial scales. The cooling distance of woodland is 330 m, much more than that of water (180 m), but the land surface temperature around water decreased more than that around the woodland within the cooling distance. In the specific urban planning cases, woodland can be designed with a complex shape, high tree planting density and large planting areas while water bodies with large patch areas to cool the densely built-up areas. The results of this study have utility for researchers, urban planners and urban designers seeking how to efficiently and reasonably rearrange landscapes with cooling effect and in urban land design, which is of great significance to improve urban heat island problem

Urban dust in the Guanzhong Basin of China, part I: A regional distribution of dust sources retrieved using satellite data

Urban dust pollution has been becoming an outstanding environmental problem due to rapid urbanization in China. However, it is very difficult to construct an urban dust inventory, owing to its small horizontal scale and strong temporal/spatial variability. With the analysis of visual interpretation, maximum likelihood classification, extrapolation and spatial overlaying, we quantified dust source distributions of urban constructions, barrens and croplands in the Guanzhong Basin using various satellite data, including VHR (0.5 m), Lansat-8 OLI (30 m) and MCD12Q1 (500 m). The croplands were the dominant dust sources, accounting for 40% (17,913 km(2)) of the study area in summer and 36% (17,913 km(2)) in winter, followed by barrens, accounting for 5% in summer and 10% in winter. Moreover, the total constructions were 126 km(2), including 84% of active and 16% inactive. In addition, 59% of the constructions aggregated on the only megacity of the study area, Xi&#39;an. With high accuracy exceeding 88%, the proposed satellite-data based method is feasible and valuable to quantify distributions of dust sources. This study provides a new perspective to evaluate regional urban dust, which is seldom quantified and reported. In a companied paper (Part-2 of the study), the detailed distribution of the urban dust sources is applied in a dynamical/aerosol model (WRF-Dust) to assess the effect of dust sources on aerosol pollution. (C) 2015 Elsevier B.V. All rights reserved

Dexmedetomidine for prevention of postoperative delirium in older adults undergoing oesophagectomy with total intravenous anaesthesia: A double-blind, randomised clinical trial.

BackgroundDexmedetomidine is known to be a sedative. Recent studies suggest that administration of dexmedetomidine can prevent postoperative delirium (POD) which has been confirmed as a common complication after major surgery. However, its effects in patients undergoing oesophagectomy are scarce.ObjectiveTo investigate the efficacy and safety of dexmedetomidine in reducing POD in elderly patients after transthoracic oesophagectomy with total intravenous anaesthesia (TIVA).DesignA randomised, double-blind, placebo-controlled trial.SettingSingle-centre, tertiary care hospital, November 2016 to September 2018.PatientsEligible patients (n = 177) undergoing transthoracic oesophagectomy were randomly assigned to receive total intravenous anaesthesia (TIVA, n = 87) or dexmedetomidine with TIVA (DEX-TIVA, n = 90).InterventionsPatients receiving DEX-TIVA received a loading dose of dexmedetomidine (0.4 μg kg-1), over 15 min, followed by a continuous infusion at a rate of 0.1 μg kg-1 h-1 until 1 h before the end of surgery. Patients receiving TIVA received physiological saline with a similar infusion rate protocol.Outcome measuresThe primary outcome was the incidence of POD. The secondary endpoints were the incidence of emergence agitation, serum interleukin-6 (IL-6) levels and haemodynamic profile.ResultsAll randomised patients were included with planned intention-to-treat analyses for POD. Delirium occurred in 15 (16.7%) of 90 cases given dexmedetomidine, and in 32 (36.8%) of 87 cases given saline (P = 0.0036). The DEX-TIVA group showed less frequent emergence agitation than the TIVA group (22.1 vs. 48.0%, P = 0.0058). The incremental change in surgery-induced IL-6 levels was greater in the TIVA group than DEX-TIVA group (P &lt; 0.0001).ConclusionAdding peri-operative dexmedetomidine to a total intravenous anaesthetic safely reduces POD and emergence agitation in elderly patients undergoing open transthoracic oesophagectomy. These benefits were associated with a postoperative reduction in circulating levels of the pro-inflammatory cytokine IL-6 and stabilisation of the haemodynamic profile.Trial registrationChinese Clinical Trials Register Identifier: ChiCTR-IPR-17010881