Bias adjustment and ensemble recalibration methods for seasonal forecasting: a comprehensive intercomparison using the C3S dataset

This work presents a comprehensive intercomparison of diferent alternatives for the calibration of seasonal forecasts, ranging from simple bias adjustment (BA)-e.g. quantile mapping-to more sophisticated ensemble recalibration (RC) methods- e.g. non-homogeneous Gaussian regression, which build on the temporal correspondence between the climate model and the corresponding observations to generate reliable predictions. To be as critical as possible, we validate the raw model and the calibrated forecasts in terms of a number of metrics which take into account diferent aspects of forecast quality (association, accuracy, discrimination and reliability). We focus on one-month lead forecasts of precipitation and temperature from four state-of-the-art seasonal forecasting systems, three of them included in the Copernicus Climate Change Service dataset (ECMWF-SEAS5, UK Met Ofce-GloSea5 and Météo France-System5) for boreal winter and summer over two illustrative regions with diferent skill characteristics (Europe and Southeast Asia). Our results indicate that both BA and RC methods efectively correct the large raw model biases, which is of paramount importance for users, particularly when directly using the climate model outputs to run impact models, or when computing climate indices depending on absolute values/thresholds. However, except for particular regions and/or seasons (typically with high skill), there is only marginal added value-with respect to the raw model outputs-beyond this bias removal. For those cases, RC methods can outperform BA ones, mostly due to an improvement in reliability. Finally, we also show that whereas an increase in the number of members only modestly afects the results obtained from calibration, longer hindcast periods lead to improved forecast quality, particularly for RC methods.This work has been funded by the C3S activity on Evaluation and Quality Control for seasonal forecasts. JMG was partially supported by the project MULTI-SDM (CGL2015-66583-R, MINECO/FEDER). FJDR was partially funded by the H2020 EUCP project (GA 776613)

Inhibition of Pediatric Glioblastoma Tumor Growth by the Anti-Cancer Agent OKN-007 in Orthotopic Mouse Xenografts

We thank the Peggy and Charles Stephenson Cancer Center at the University of Oklahoma, Oklahoma City, OK, for funding, who received an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under grant number P20 GM103639 for the use of the Histology and Immunohistochemistry Core for providing immunohistochemistry and photographic services. This work was also supported by Oklahoma State University, Center of Veterinary Health Science (Support Grant AE-1-50060 to P.C.S.), the Musella Foundation (R.A.T.), and the Childhood Brain Tumor Foundation (R.A.T.).Pediatric glioblastomas (pGBM), although rare, are one of the leading causes of cancer-related deaths in children, with tumors essentially refractory to existing treatments. Here, we describe the use of conventional and advanced in vivo magnetic resonance imaging (MRI) techniques to assess a novel orthotopic xenograft pGBM mouse (IC-3752GBM patient-derived culture) model, and to monitor the effects of the anti-cancer agent OKN-007 as an inhibitor of pGBM tumor growth. Immunohistochemistry support data is also presented for cell proliferation and tumor growth signaling. OKN-007 was found to significantly decrease tumor volumes (p<0.05) and increase animal survival (p<0.05) in all OKN-007-treated mice compared to untreated animals. In a responsive cohort of treated animals, OKN-007 was able to significantly decrease tumor volumes (p<0.0001), increase survival (p<0.001), and increase diffusion (p<0.01) and perfusion rates (p<0.05). OKN-007 also significantly reduced lipid tumor metabolism in responsive animals (Lip1.3 and Lip0.9)-to-creatine ratio (p<0.05), as well as significantly decrease tumor cell proliferation (p<0.05) and microvessel density (p<0.05). Furthermore, in relationship to the PDGFRα pathway, OKN-007 was able to significantly decrease SULF2 (p<0.05) and PDGFR-α (platelet-derived growth factor receptor-α) (p<0.05) immunoexpression, and significantly increase decorin expression (p<0.05) in responsive mice. This study indicates that OKN-007 may be an effective anti-cancer agent for some patients with pGBMs by inhibiting cell proliferation and angiogenesis, possibly via the PDGFRα pathway, and could be considered as an additional therapy for pediatric brain tumor patients.Yeshttp://www.plosone.org/static/editorial#pee

Global variation in anastomosis and end colostomy formation following left-sided colorectal resection

Background End colostomy rates following colorectal resection vary across institutions in high-income settings, being influenced by patient, disease, surgeon and system factors. This study aimed to assess global variation in end colostomy rates after left-sided colorectal resection. Methods This study comprised an analysis of GlobalSurg-1 and -2 international, prospective, observational cohort studies (2014, 2016), including consecutive adult patients undergoing elective or emergency left-sided colorectal resection within discrete 2-week windows. Countries were grouped into high-, middle- and low-income tertiles according to the United Nations Human Development Index (HDI). Factors associated with colostomy formation versus primary anastomosis were explored using a multilevel, multivariable logistic regression model. Results In total, 1635 patients from 242 hospitals in 57 countries undergoing left-sided colorectal resection were included: 113 (6·9 per cent) from low-HDI, 254 (15·5 per cent) from middle-HDI and 1268 (77·6 per cent) from high-HDI countries. There was a higher proportion of patients with perforated disease (57·5, 40·9 and 35·4 per cent; P < 0·001) and subsequent use of end colostomy (52·2, 24·8 and 18·9 per cent; P < 0·001) in low- compared with middle- and high-HDI settings. The association with colostomy use in low-HDI settings persisted (odds ratio (OR) 3·20, 95 per cent c.i. 1·35 to 7·57; P = 0·008) after risk adjustment for malignant disease (OR 2·34, 1·65 to 3·32; P < 0·001), emergency surgery (OR 4·08, 2·73 to 6·10; P < 0·001), time to operation at least 48 h (OR 1·99, 1·28 to 3·09; P = 0·002) and disease perforation (OR 4·00, 2·81 to 5·69; P < 0·001). Conclusion Global differences existed in the proportion of patients receiving end stomas after left-sided colorectal resection based on income, which went beyond case mix alone