Mitochondrial ghost lineages blur phylogeography and taxonomy of Natrix helvetica and N. natrix in Italy and Corsica

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Greenland Temperature Response to Climate Forcing during the Last Deglaciation

Greenland ice core water isotopic composition (δ¹⁸O) provides detailed evidence for abrupt climate changes, but is by itself insufficient for quantitative reconstruction of past temperatures and their spatial patterns. We investigate Greenland temperature evolution during the last deglaciation using independent reconstructions from three ice cores and simulations with a coupled ocean-atmosphere climate model. Contrary to the traditional δ¹⁸O interpretation, the Younger Dryas period was 4.5±2°C warmer than the Oldest Dryas, due to increased CO₂ forcing and summer insolation. The magnitude of abrupt temperature changes is larger in central Greenland (9-14°C) than in the northwest (5-9°C), fingerprinting a North-Atlantic origin. Simulated changes in temperature seasonality closely track changes in the Atlantic overturning strength, and support the hypothesis that abrupt climate change is mostly a winter phenomenon

The IASLC Lung Cancer Staging Project: A Renewed Call to Participation

Over the past two decades, the International Association for the Study of Lung Cancer (IASLC) Staging Project has been a steady source of evidence-based recommendations for the TNM classification for lung cancer published by the Union for International Cancer Control and the American Joint Committee on Cancer. The Staging and Prognostic Factors Committee of the IASLC is now issuing a call for participation in the next phase of the project, which is designed to inform the ninth edition of the TNM classification for lung cancer. Following the case recruitment model for the eighth edition database, volunteer site participants are asked to submit data on patients whose lung cancer was diagnosed between January 1, 2011, and December 31, 2019, to the project by means of a secure, electronic data capture system provided by Cancer Research And Biostatistics in Seattle, Washington. Alternatively, participants may transfer existing data sets. The continued success of the IASLC Staging Project in achieving its objectives will depend on the extent of international participation, the degree to which cases are entered directly into the electronic data capture system, and how closely externally submitted cases conform to the data elements for the project

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

Implementation of counted layers for coherent ice core chronology

International audienceA recent coherent chronology has been built for four Antarctic ice cores and the NorthGRIP (NGRIP) Greenland ice core (Antarctic Ice Core Chronology 2012, AICC2012) using a Bayesian approach for ice core dating (Datice). When building the AICC2012 chronology, and in order to prevent any confusion with official ice core chronology, the AICC2012 chronology for NGRIP was forced to fit exactly the GICC05 chronology based on layer counting. However, such a strong tuning did not satisfy the hypothesis of independence of background parameters and observations for the NGRIP core, as required by Datice. We present here the implementation in Datice of a new type of markers that is better suited for constraints deduced from layer counting: the duration constraints. Estimating the global error on chronology due to such markers is not straightforward and implies some assumption on the correlation between individual counting errors for each interval of duration. We validate this new methodological implementation by conducting twin experiments and a posteriori diagnostics on the NGRIP ice core. Several sensitivity tests on marker sampling and correlation between counting errors were performed to provide some guidelines when using such a method for future dating experiments. Finally, using these markers for NGRIP in a five-core dating exercise with Datice leads to new chronologies that do not differ by more than 410 years from AICC2012 for Antarctic ice cores and 150 years from GICC05 for NGRIP over the last 60 000 years

CO2 and O2/N2 variations in and just below the bubble–clathrate transformation zone of Antarctic ice cores

CO2 measurements on the EPICA (European Project for Ice Coring in Antarctica) DML ice core in depth levels just below the bubble ice–clathrate ice transformation zone (1230–2240 m depth) were performed. In the youngest part (1230–1600 m), they reveal variations of up to 25 ppmv around the mean atmospheric concentration within centimetres, corresponding to a snow deposition interval of a few years. Similar results are found at corresponding depth regions of the Dome C and the Talos Dome ice cores. Since we can exclude all hitherto known processes altering the concentration of CO2 in ice cores, we present a hypothesis about spatial fractionation of air components related to episodically increasing clathrate formation followed by diffusion processes from bubbles to clathrates. This hypothesis is supported by optical line-scan observations and by O2/N2 measurements at the same depth where strong CO2 variations are detected. Below the clathrate formation zone, this small-scale fractionation process is slowly smoothed out, most likely by diffusion, regaining the initial mean atmospheric concentration. Although this process compromises the representativeness of a single CO2 measurement on small ice samples in the clathrate formation zone of an ice core, it does not affect the mean atmospheric CO2 concentration if CO2 values are averaged over a sufficiently long depth scale (> 10 cm in case of the EPICA DML ice core)

The IASLC mesothelioma staging project: proposals for revisions of the n descriptors in the forthcoming eighth edition of the TNM classification for pleural mesothelioma

INTRODUCTION Nodal categories for malignant pleural mesothelioma are derived from the lung cancer staging system and have not been adequately validated. The International Association for the Study of Lung Cancer developed a multinational database to generate evidence-based recommendations to inform the eighth edition of the TNM classification of malignant pleural mesothelioma. METHODS Data from 29 centers were entered prospectively (n = 1566) or by transfer of retrospective data (n = 1953). Survival according to the seventh edition N categories was evaluated using Kaplan-Meier survival curves and Cox proportional hazards regression analysis. Survival was measured from the date of diagnosis. RESULTS There were 2432 analyzable cases: 1603 had clinical (c) staging, 1614 had pathologic (p) staging, and 785 had both. For clinically staged tumors there was no separation in Kaplan-Meier curves between cN0, cN1 or cN2 (cN1 versus cN0 hazard ratio [HR] = 1.06, p = 0.77 and cN2 versus cN1 HR = 1.04, p = 0.85). For pathologically staged tumors, patients with pN1 or pN2 tumors had worse survival than those with pN0 tumors (HR = 1.51, p < 0.0001) but no survival difference was noted between those with pN1 and pN2 tumors (HR = 0.99, p = 0.99). Patients with both pN1 and pN2 nodal involvement had poorer survival than those with pN2 tumors only (HR = 1.60, p = 0.007) or pN0 tumors (HR = 1.62, p < 0.0001). CONCLUSIONS A recommendation to collapse both clinical and pN1 and pN2 categories into a single N category comprising ipsilateral, intrathoracic nodal metastases (N1) will be made for the eighth edition staging system. Nodes previously categorized as N3 will be reclassified as N2